Seven endurance exercise-trained subjects were studied 12, 21, 56, and 84 days after cessation of training. Maximal O2 uptake (VO2 max) declined 7% (P less than 0.05) during the first 21 days of inactivity and stabilized after 56 days at a level 16% (P less than 0.05) below the initial trained value. After 84 days of detraining the experimental subjects still had a higher VO2 max than did eight sedentary control subjects who had never trained (50.8 vs. 43.3 ml X kg-1 X min-1), due primarily to a larger arterial-mixed venous O2 (a-vO2) difference. Stroke volume (SV) during exercise was high initially and declined during the early detraining period to a level not different from control. Skeletal muscle capillarization did not decline with inactivity and remained 50% above (P less than 0.05) sedentary control. Citrate synthase and succinate dehydrogenase activities in muscle declined with a half-time of 12 days and stabilized at levels 50% above sedentary control (P less than 0.05). The initial decline in VO2 max was related to a reduced SV and the later decline to a reduced a-vO2 difference. Muscle capillarization and oxidative enzyme activity remained above sedentary levels and this may help explain why a-vO2 difference and VO2 max after 84 days of detraining were still higher than in untrained subjects.