Effects of chronic intraventricular administration of nerve growth factor (NGF, 1 microgram qod for 21 days) on weight gain, hypothalamic neuropeptide levels and choline acetyltransferase (ChAT) activity were determined in adult female Wistar rats. Rats chronically treated with cytochrome c (cc) gained 163 g over the 21 day treatment schedule, whereas NGF-treated rats only gained 110 g. Thus, NGF-treated rats gained 53 g less; this change in weight gain is equivalent to approximately a 20% decrease of total weight gain compared to the cc-treated control rats. Chronic NGF treatment significantly decreased hypothalamic cholecystokinin (CCK) levels by 24% (P = 0.0070), but did not alter either hypothalamic neuropeptide Y (NPY) or bombesin (BOMB) levels (98% and 105% of cc-treated control levels, respectively). In addition, chronic NGF treatment did not significantly alter hypothalamic ChAT activity (95% of cc-treated control rats). The results of the present study suggest that NGF-induced decreases in weight gain are not the result of alterations of hypothalamic cholinergic function. However, it is possible that NGF-induced alterations of hypothalamic CCK synthesis and release may be involved in the NGF-induced decrease in weight gain.