The responses of whole body, skeletal muscle, and plasma to oral K loading were studied in K-depleted male rats. Potassium depletion was induced by feeding the rats a K-deficient diet for 4 wk and injecting deoxycorticosterone acetate during the first week. After 4 wk, the rats were growth retarded and hypokalemic (1.9 mmol/l plasma) and had low whole-body and muscle K content, 188 +/- 27 and 276 +/- 19 mmol/kg fat-free dried tissue (FFDT), respectively, compared with 296 +/- 10 and 454 +/- 13 mmol/kg FFDT for the control group. Sodium and water retention also occurred in the K-deficient group. After K depletion, the rats were divided into four groups and received either 0, 1, 2, or 3 intragastric doses of 10 mmol KCl/kg at 8-h intervals. The rats were killed 8 h after the last dose. Control rats were treated similarly. K-depleted and control rats responded differently to K loading. In the normal rats, plasma K remained at 5.0 +/- 0.5 mmol/l, muscle K increased to 502 +/- 24 mmol/kg, and muscle K/N ratio increased from 3.0 to 3.4 mmol/g. In the K-depleted rats, plasma K increased to 7.2 +/- 0.7 mmol/l, muscle K increased to 453 +/- 50 mmol/kg, and muscle K/N ratio increased from 1.8 to 3.1 mmol/g. These data indicate that the capacity of the muscles to accumulate K was impaired after severe K depletion and caused elevated plasma K levels when repletion was complete.