Abstract The present study was designed to identify specific and sensitive compounds which may act as specific inhibitors of pheromone biosynthesis in the moth Helicoverpa armigera using physiological bioassays and three-dimentional quantitative structure–activity relationship studies. Twenty-eight octopamine agonists were initially screened using an in vivo bioassay for pheromone production by female moths. Fourteen compounds were found to inhibit pheromone production in the moths to a level of 50% or more and were subsequently used in dose-response studies to determine ID 5s. The dose-response studies were performed in vitro, analyzing the effect of these compounds on intracellular cAMP production as well as on the de novo pheromone biosynthesis. Six active derivatives, with activity in the nanomolar range, were identified with the following order of decreasing pheromonostatic activity: 2-(2, 6-dimethylanilino)imidazolide > 2-(2-methyl-4-chloroanilino)oxazolidine > clonidine > 2-(2,6-diethylanilino) thiazolidine > 2-(3,5-dichloroben zylamino)-2-oxazoline > tolazoline. Six other compounds were less active, with ID 5s in the micromolar range. The active compounds were utilized for the development of a predictive model using physicochemical parameters. The results of the present study indicate that these derivatives could provide useful information in the characterization and differentiation of octopaminergic receptor types and subtypes.