Cardiac sarcoplasmic reticulum (SR) ATP-dependent Ca2+-uptake was found to be depressed in 4 month streptozotocin-induced diabetic rats. Calmodulin, cAMP-dependent protein kinase and K+ stimulated Ca2+-uptake to similar degrees in SR from both control diabetic rats. Long chain acylcarnitine (7 microM) decreased Ca2+-transport in control rats by 46% but only 26% in diabetic animals. The data suggests that the depression in cardiac SR Ca2+-uptake activity in diabetic rats is non-specific in origin and not a result of alterations in regulation of SR function.