Combined treatment with GDNF and BDNF produces an additive increase in dopaminergic PG neuron survival in vitro at subsaturating, but not saturating, concentrations of each factor. E16.5 rat PG dissociate cultures were grown for 3 d in the absence (Con) or presence of GDNF alone (GDNF), BDNF alone (BDNF), or both GDNF and BDNF (Both) and then immunostained for TH. At 5 ng/ml of each factor (A), TH⁺ neuron survival was increased 9-, 19-, and 28-fold in the presence of GDNF, BDNF, and GDNF plus BDNF, respectively, compared with control cultures. In contrast, at 100 ng/ml of each factor (B), there was no additive effect on survival of GDNF plus BDNF above the level seen in the presence of BDNF alone. Bars represent means ± SEM of at least six cultures per group. *p < 0.05; **p < 0.01; ns, not significant.