We compared the time course of saturated phosphatidylcholine secretion and cellular cyclic AMP concentrations in isolated rat alveolar type II cells following stimulation by cholera toxin, terbutaline, and 12-0-tetradecanoyl-13-phorbol acetate. Secretion of saturated phosphatidylcholine was stimulated by cholera toxin at concentrations from 1.2 X 10(-11) M to 5.0 X 10(-7) M. In time course experiments there was no significant stimulation with cholera toxin before 1 hr; all subsequent points between 90 and 180 min were significantly different from controls. Secretion stimulated by 10 microM terbutaline was similar in magnitude to stimulation by 1.2 X 10(-9) M cholera toxin; stimulation following either of these agonists was higher than control secretion and lower than secretion stimulated by 10 nM 12-0-tetradecanoyl-13-phorbol acetate. Terbutaline caused an early rise in cellular cyclic AMP that peaked within 5 min and then returned to basal level by 60 min. In contrast, cholera toxin did not increase cellular cAMP levels until 60 min after addition, but then produced a sustained increase in cyclic AMP levels for up to 3 hr. In conclusion, we have presented evidence that more than one mechanism exists by which secretion can be stimulated in type II cells. It is likely that both terbutaline and cholera toxin act by stimulating cellular cyclic AMP and that 12-0-tetradecanoyl-13-phorbol acetate acts by a mechanism different from terbutaline or cholera toxin.