We examined the effects of P1 purinoceptor agonists on secretion of phosphatidylcholine in primary cultures of rat type II pneumocytes. Adenosine and its nonmetabolizable analogs, 5'-N-ethylcarboxyamidoadenosine (NECA), N6-phenylisopropyladenosine (PIA) and 2-chloroadenosine, increased secretion, and this effect was dependent on concentration. At the highest concentration, all agonists stimulated phosphatidylcholine secretion approximately 2-fold. NECA, with an EC50 of 8.9 X 10(-8) M, was the most potent agonist. The order of potency was NECA greater than 2-chloroadenosine = L-PIA greater than or equal to adenosine greater than D-PIA. The stimulatory effect of 10(-6) M NECA was diminished by the P1 antagonists theophylline and 8-phenyltheophylline. The degree of stimulation by the adenosine analogs as well as its time course was the same as that induced by terbutaline. The effects of the adenosine analogs and of terbutaline were not additive, suggesting a similar mode of action for the beta adrenergic and purinoceptor agonists. Terbutaline and the adenosine analogs increased intracellular cyclic AMP levels. Again, NECA was the most potent adenosine analog. For NECA, L-PIA and adenosine, there was a significant correlation between effects on secretion and on cyclic AMP content. These data suggest that the effect of adenosine on phosphatidylcholine secretion in type II pneumocytes is mediated by the A2 subtype of the P1 purinoceptor.