An examination of the effects of 250 or 1500 micrograms m-3 concentrations of diesel particulate from diesel exhaust on the activity of adenylate or guanylate cyclase was undertaken using liver and lung tissue of rats and guinea pigs. These membrane and cytosolic enzymes were selected to screen for functional or regulatory alterations in these tissues. The studies for adenylate cyclase used the microsomal membrane fraction of each tissue; for guanylate cyclase, the microsomal membrane and supernate fractions were used. Basal and fluoride-stimulated adenylate cyclase activity were measured. Basal and sodium azide-stimulated guanylate cyclase activity were also determined. The basal activity of rat liver adenylate cyclase is generally unchanged throughout 52 weeks of diesel exposure. Stimulated adenylate cyclase shows an age-related decrease for all animal treatments throughout the study. Changes in enzyme activity occurred at 12 weeks and 52 weeks after 1500 micrograms m-3 exposure. Soluble stimulated guinea pig lung guanylate cyclase was first increased (6 weeks) and then decreased (24 weeks) by diesel exposure. At 52 weeks, there was no change. The data suggest the following trends: (1) an increased basal adenylate cyclase in the rat lung; (2) an age-related decrease in adenylate cyclase activity in rat liver, and (3) a biphasic exposure-related response of soluble guanylate cyclase for the guinea pig lung during the first 24 weeks, but no change at 52 weeks. In general, however, these studies suggest that diesel exposure does not substantially alter either of these intracellular regulating enzymes.