Albumin synthesis was evaluated in 5 young adult males (19-25 yr) and 6 elderly males (64-78 yr) by a procedure involving oral administration of 15N-glycine every 3 hr over a 60-hr period. From about 40 hr onwards, urinary urea achieved a plateau of 15N-enrichment, which was estimated from the average of the last five (low protein) or seven (adequate protein) consecutive three-hourly urinary samples of the 60-hr period. This enrichment plateau was used as an index of the 15N-enrichment of the guanidine N of hepatic free arginine. The 15N-enrichment of the guanidine N of arginine in serum albumin was determined and albumin synthesis was estimated by comparing this value with the estimated enrichment of precursor hepatic arginine. Using this methodology, serum albumin concentration, synthesis, rate and plasma volume were measured when the young and elderly subjects had received an adequate protein intake (1.5 g x kg-1 for 7 days) or a low protein intake (0.4 g x kg-1 for 14 days). Serum albumin concentration was lower in the elderly at both levels of protein intake; protein intake did not affect this parameter in either age-group. Plasma volume (per kg body weight) did not differ between young and old, but increased in both groups when they were given the low-protein diet, so that the total intravascular albumin mass increased in both age groups significantly in the case of the young, and was probably due to net transfer of albumin from the extravascular pool. The fractional synthesis rate of the whole body albumin pool with adequate intake of protein was 4.0%/day in the young and 3.4%/day in the elderly. This fractional rate was reduced significantly by giving the low-protein diet to the young subjects, but was not reduced in the elderly. Absolute synthesis rates, calculated per kg body weight and per kg body cell mass, led to a similar conclusion. Whole body protein synthesis was also estimated from urinary 15N-urea enrichment using the Picou and Taylor-Roberts model. Albumin synthesis as a percentage of whole body protein synthesis (5%-6%) was reduced in the young adults by giving the low-protein diet, but was unchanged in the elderly. In conclusion, the rate of albumin synthesis in the young, but not in the elderly, is sensitive to changes in protein intake. It is suggested that albumin synthesis in the elderly is controlled at a lower set point, which prevents its response to higher protein intakes.