WE studied the trophic requirements of neonatal rat sensory neurons in single neuron and standard culture (9400 neurons/cm2). In agreement with previous studies, we found that survival of sensory neurons in standard culture is strictly dependent on nerve growth factor (NGF). Contrary to this, however, no difference between NGF-treated and untreated cultures with respect to survival and neurite formation was evident when neurons were plated as single cells. Approximately 70% of singly-seeded sensory neurons survived for 2 days independent of supply with NGF. Survival of large, mid-sized, and small sensory neurons in single neuron culture demonstrated that this phenomenon is not confined to a neuronal subpopulation. We speculate that survival in single neuron culture is due to the absence or inactivation of yet unidentified cell death-inducing factors that in standard culture are overridden or suppressed by NGF.