Studies of the regulation of Ca2 ion upatake by sarcoplasmic reticulum from young and aged animals were extended to include the effects of treatment with cyclic AMP and protein kinase. Results show that following treatment with cyclic AMP saroplasmic reticulum isolated from young hearts exhibits greater activity than membranes prepared from aged hearts. The percent increase in response to cyclic AMP was the same in both age groups indicating that the mechanism for mediating the response is unaltered with age. Measurements of the passive permeability to Ca2 ion and phosphoenzyme level associated with Ca2 ion transport in saroplasmic reticulum from young and old hearts indicate that differences in maximum velocity of accumulation reflect changes in turnover rate rather than in passive leak or in site density. Comparative investigation of the ATPase partial reactions in the Ca2 ion and Na ion plus K ion pumps provide evidence that cation-induced slow conformational changes control the overall enzyme activity.