Nicotinic acetylcholine (ACh) currents were studied in cultured postnatal rat hippocampal neurons, using whole-cell voltage-clamp techniques. In most cells, ACh produces one of two types of response. One class of ACh currents exhibits rapid and profound desensitization and is sensitive to inhibition by alpha-bungarotoxin (alpha BTXN). The second class activates slowly and exhibits no desensitization during prolonged agonist applications. This slow current is insensitive to alpha BTXN. Both the fast and slow responses exhibit inwardly rectifying current-voltage relationships and pass little current at positive membrane potentials. Both currents can be recorded in the presence of 1 microM atropine but are blocked by 0.1-1.0 mM d-tubocurarine and 0.1-1.0 mM mecamylamine. These observations suggest heterogeneity of nicotinic ACh receptors in rat hippocampal neurons and provide support for functional alpha BTXN-sensitive nicotinic receptors in this region.