A variety of agents stimulate the chloride-dependent short-circuit current (Isc) across isolated locust recta. In this study, the role of cyclic nucleotides in mediating this stimulation was examined by measuring levels of cyclic AMP and cyclic GMP in tissues exposed to these agents. After bathing recta in saline, there is a decline in I,, and this is accompanied by a fall in cellular levels of cyclic AMP and cyclic Gl". Stimulants of I, across locust recta, corpus cardiacum (CC) extracts containing chloride transport-stimulating hormone (CTSH) and forskolin, also elevate cellular levels of cyclic AMP. Between 5 and 10 min after addition of CC extract, there is an increase in cyclic AMP levels. During this same time period, the I, rises at its maximal rate. The I, remains elevated for at least another 20 min, even though tissue cyclic-AMP levels decline rapidly by 15 min. These results suggest that stimulation of I , , is induced by a rise in cyclic AMP, but the cessation of stimulated active ion transport is controlled by other biochemical processes. In contrast to the relatively rapid rise in cyclic-AMP levels, a 60-min exposure to CC extract was required to elicit a rise in cyclic GMP, and therefore it may not be involved in the early stages of I, stimulation.