The effects of basic fibroblast growth factor and nerve growth factor on survival and transmitter expression of cultured rat embryonic (E18) septal neurons were studied. Two different culture media were used: (i) a horse serum-containing Leibowitz L-15 medium and (ii) a serum-free N1-supplemented Dulbecco's modified Eagle's medium. Addition of basic fibroblast growth factor to either culture medium enhanced neuronal survival in low density cultures after 4 days. The effects of basic fibroblast growth factor were dose-dependent and blocked by anti-basic fibroblast growth factor antibodies. In serum-containing L-15 medium nerve growth factor also promoted neuronal survival. Basic fibroblast growth factor and nerve growth factor supported neurons comprised both cholinergic and GABAergic subpopulations. The effects of basic fibroblast growth factor and nerve growth factor were not additive. In high density cultures using serum-containing L-15 medium survival of septal neurons was four times higher than in low density cultures after 4 days. Addition of basic fibroblast growth factor or nerve growth factor did not further augment neuronal survival in high density cultures. Maintenance of septal neurons at high density was not affected by antibodies to basic fibroblast growth factor and/or nerve growth factor. Addition of basic fibroblast growth factor or nerve growth factor to serum-containing L-15 medium at high cell density significantly enhanced choline acetyltransferase activity 3- and 7.5-fold, respectively, without affecting cell survival. In conclusion, next to nerve growth factor, basic fibroblast growth factor, which has been located in the hippocampal target area of septal neurons, appears to be another potent trophic factor for septal neurons.