The effects of dibutyryl cAMP, 8-bromo-cGMP, 3-isobutyl-1-methyl xanthine (MIX) and isoproterenol were examined. When administered simultaneously with acetylcholine (10(-6) M) in concentrations of 10(-5) M, both isoproterenol and cAMP reduced fluid secretion (16 and 31 per cent, respectively) and enhanced the decay in rate of flow with time, while cGMP and MIX increased salivary volumes (25 and 19 per cent, respectively). Isoproterenol-decreased Na and Cl and increased K and residual anion concentrations. These effects, except for increased K, were also observed with MIX, cAMP and cGMP did not significantly affect cation concentrations but reduced Cl and increased residual anion, although to a lesser extent than isoproterenol or MIX. The cyclic nucleotides did not affect the flow of saliva when added to the perfusate for 40 min after 40 min of acetylcholine stimulation. Prior exposure to cGMP increased the volume of saliva secreted after re-exposure to acetylcholine alone and both cGMP and cAMP increased the Na and reduced the K concentration of the stimulated secretion. These results suggest that cyclic nucleotides are involved in salivary fluid and electrolyte secretion and can modulate the effects of cholinergic stimuli. cGMP may be involved mainly in fluid secretion and, as salivary fluid originates almost exclusively in salivary acini, it may exert its action in acinar cells and activate specific components of the mechanism of primary secretion. cAMP may be primarily involved in transductal electrolyte transport, and may also inhibit certain parts of the fluid secretory mechanism, or reduce the effectiveness of cholinergic stimuli in activating them.(ABSTRACT TRUNCATED AT 250 WORDS)