The dietary supplement, beta-hydroxy-beta-methylbutyrate (HMB), has been shown to decrease muscle proteolysis during the stress of exercise and disease. The aim of this investigation was to determine the time course kinetics of HMB and to determine whether oral glucose ingestion alters the kinetics. In Study 1, eight males (32 +/- 10 yrs) participated in two randomize trials: 1) oral ingestion of 1g of HMB with water in capsule form (HMB), and 2) placebo. Blood samples were obtained prior to ingestion of treatment and at 30, 60, 90, 120, 150, and 180 min for the measurement of plasma HMB. Additional blood samples were obtained at 6, 9, and 12 hr. Urine was collected prior to ingestion and at 3, 6, 9, and 12 h for the measurement of urinary HMB. In Study 2, eight males (25 +/- 6 yrs) followed the same study design and testing procedure as for Study 1. Treatments were 1) modified glucose tolerance test (75 g glucose) (GLU), 2) oral ingestion of 3 g of HMB with water (HMB), and 3) ingestion of 3 g of HMB with 75 g of glucose (HMB+GLU). Blood samples were analyzed for insulin, glucose, and HMB. Additional blood samples were obtained at 24h and 36h for the measurement of HMB. Additional urine samples were collected at 24h and 36h. In Study 1, plasma HMB peaked at 120 nmol/ml at 2.0 +/- 0.4 hr in HMB trial. Half-life was 2.37 +/- 0.1 hr. Following the consumption of 1g of HMB, approximately 14% of the HMB consumed accumulated in the urine. In Study 2, plasma glucose and insulin levels were significantly greater in GLU and HMB+GLU treated subjects compared to HMB treated subject at minutes 30, 60 and 90. Plasma HMB peaked at 487.9 +/- 19.0 nmol/ml at 1.0 +/- 0.1 hr in the HMB treated subjects and at 352.1 +/- 15.3 nmol/ml at 1.94 +/- 0.2 hr when subjects consumed HMB+GLU. The time to reach peak was different (P <0.001) between HMB and HMB+GLU. The plasma HMB half-life was less (P = 0.08) 2.38 +/- 0.1 hr in HMB trial compared to 2.69 +/- 0.2 hr in HMB+GLU trial. Area under the plasma HMB curve during the first 3 hr was less (P = 0.002) in the HMB+GLU trial compared to the HMB trial. From 3 h through 36 h the area under the HMB curve tended to be less (P = 0.106) for the HMB+GLU compared to the HMB alone. HMB accumulation in the urine as well as the area under the curve were similar with both HMB (94875.8 +/- 15159.5 nmol/36 hrs) and HMB+GLU (80678.2 +/- 3863.1 nmol/36 hrs). The percentage of the HMB dose that accumulates in the urine was 27% for HMB+GLU and 29% for HMB alone. In conclusion, HMB plasma levels peak within 60 to 120 min depending on the amount of HMB consumed and whether glucose is consumed with HMB. The plasma half-life is approximately 2.5 hr. Plasma HMB reaches baseline levels at approximately 9 hr following ingestion. However, 70 to 85% of the ingested oral HMB is retained in the body for further metabolism.