To examine the effects of exhaustive swimming in normal and myopathic hamsters on muscle mitochondrial Ca2+ metabolism, sedentary normal and BIO 14.6 dystrophic Syrian hamsters swam individually in 35 degree C water until exhaustion occurred. Although the normal hamsters swam three times longer than did the BIO 14.6 hamsters, both swimming groups had a comparable two-fold increase in blood lactate. Contrary to exhaustive running, exhaustive swimming did not significantly affect mitochondrial Ca2+ uptake in either cardiac or skeletal muscle, regardless of the disease state. However, in general, the coefficients of variation for mitochondrial Ca2+ metabolism increased as a function of exercise, with the BIO 14.6 swimmers more variable than the normal swimmers. This suggests that the mitochondrial Ca2+ uptake process may be affected in some manner by exhaustive swimming, so that deviations from the norm are more apparent. The results provide further evidence that mitochondrial Ca2+ metabolism adapts to the specific type of exercise utilized to produce exhaustion.