Diphenhydramine HCl (DH) and caffeine are commonly detected contaminants in waterways and drinking water nationwide (U.S.A.) and yet little is known of their influence on the development of aquatic molluscs. The antihistamine diphenhydramine blocks the chemical effects of histamine by inhibiting the re-uptake of serotonin (5-HT). Caffeine can influence the regulation of calcium (Ca² ) and neurotransmitters, such as 5- HT, by inhibiting the re-uptake of adenosine. Serotonin receptor-mediated signaling is key during embryonic development in the freshwater snail Helisoma trivolvis (Say 1816). Embryonic development rates of H. trivolvis depend upon external conditions such as oxygen concentration and temperature. We examine the effects of diphenhydramine (DH) and caffeine on development and reproductive potential of this common aquatic snail. Concentrations of DH at 40.0, 50.0 and 60.0 µM affect the in-capsule embryonic development and hatching rate. Caffeine at 40.0, 50.0 and 60.0 µM show no influence to the hatching rates; however, these caffeine concentrations influence the in-capsule embryonic rotation rate. Eight-month observations of adult H. trivolvis reproductive activities show no influence in number of egg masses deposited when exposed to test concentrations of DH or caffeine.