Cardiac adenylate cyclase activity was examined in mice treated chronically with doxorubicin. Mice received a subcutaneous dose of either 2 or 4 mg/kg doxorubicin twice weekly for 5 weeks. Mice were sacrificed five weeks after the last injection. Basal cardiac adenylate cyclase activity was significantly elevated in both the 2 and 4 mg/kg DXR-treated groups over the control level. GTP, isoproterenol (plus GTP), NaF, and forskolin stimulated activities in both the 2 and 4 mg/kg DXR-treated groups were also significantly elevated over control levels.