Several aspects of cyclic AMP second messenger signal generation were examined in EBV-transformed cell lines from 12 schizophrenic patients and 12 age- and sex-matched controls. No evidence was obtained suggesting a heritable abnormality in cyclic AMP synthesis in schizophrenia. Basal, forskolin, A1/NaF- and GppNHp-stimulated cyclic AMP synthesis in membranes from transformed cell lines was identical for schizophrenic and control subjects. In addition, no significant differences were observed for basal, forskolin-, isoproterenol- and prostaglandin E1-stimulated cyclic AMP accumulation in intact cell lines derived from ten of the schizophrenic patients compared with cell lines derived from ten of the control subjects.