Odorant specificity to l-alpha-amino acids was determined for 245 olfactory bulb (OB) neurons recorded from 121 channel catfish. The initial tests included 4 amino acids representing acidic [monosodium glutamate (Glu)], basic [arginine (Arg)], and neutral [possessing short: alanine (Ala) and long: methionine (Met) side chains] amino acids that were previously indicated to bind to independent olfactory receptor sites. Ninety-one (37%) units (Group I) tested at 1, 10, and 100 microM showed high selectivity and were excited by only one of the 4 amino acids. Odorant specificity for the vast majority of Group I units did not change over the 3 s of response time analyzed. A total of 154 OB units (63%) (Group II) were excited by a second amino acid, but only at >/=10x odorant concentration. An additional 69 Group I units were tested with related amino acids and derivatives from 10(-9) to 10(-5) M to determine their excitatory odorant thresholds and selectivities. Two groups of units originally selective for Met were evident: those most sensitive to neutral amino acids having branched and linear side chains, respectively. OB units originally selective for Ala responded at low concentration to other similar amino acids. Units originally selective for Arg were excited at low concentration by amino acids possessing in their side chains at least 3 methylene groups and a terminal amide or guanidinium group. The specificities of the OB units determined electrophysiologically are sufficient to account for many of the previous results of behavioral discrimination of amino acids in this and related species.