Abstract The direct effects of tepp, methyl paraoxon, DDT, dieldrin, aldicarb, dimetilan, rotenone, allethrin, and oxythioquinox were surveyed on cockroach brain adenyl cyclase and phosphodiesterase in vitro. The most striking result of this survey was the observation that oxythioquinox is a potent inhibitor of phosphodiesterase. The inhibitory activities of seven different quinoxalinedithiol derivatives were compared with those of methyl-xanthines and SQ 65,442 on phosphodiesterases from cockroach brain, rat brain, and beef heart. Although I 50 values of the quinoxaline inhibitors were found to be in the μ M range, solubility deficiencies apparently limit their effectiveness with inhibition reaching limiting values of about 70–90% as concentrations are increased. Evaluation of the quinoxaline inhibitors to enhance the accumulation of cyclic AMP in the assay of adenyl cyclase did not demonstrate any significant advantage over the use of aminophylline, a standard inhibitor for this purpose. A new assay for phosphodiesterase, involving separation of substrate from product on aluminum oxide columns, was developed by modification of similar techniques utilized in the assay of adenyl cyclase.