The present experiments examined the impact of manipulating the NO system on production of isolation-induced ultrasonic vocalizations (USVs) in 10- and Ii-day-old rat pups. Pups were tested under both high- and low-baseline USV emission: the latter was accomplished by pretest administration of cocaine, a drug known to suppress USVs. Treatment with 10, 50, or 100 mg/kg (but not 1 mg/kg) of the nitric oxide synthase (NOS) inhibitor L-nitro-arginine methyl ester (L-NAME) significantly attenuated USV production, as did injection of 10 mg/kg cocaine; combined treatment with both drugs did not result in greater suppression, perhaps due to a floor effect. Although cocaine increased locomotor activity, treatment with L- or D-NAME alone did not alter activity levels. Exposure to L-NAME induced some hypothermia, although these alterations in body temperature were not systematically related to the drug-induced suppression of USVs. Alterations in USV production by L-NAME were not evident after pretreatment with the less active isomer D-NAME, evidence supporting the importance of NO synthesis inhibition per se in the marked L-NAME-induced suppression of USVs in isolated infant rats. (C) 1999 Elsevier Science Inc.