The response of dorsal root ganglia (DRG) neurons to NGF deprivation and to axotomy was examined in adult guinea pigs. The success of NGF deprivation by means of an autoimmune approach was monitored by the measurement of serum antibody titer levels against guinea pig NGF with the standard bioassay for NGF activity. That the antibody produced NGF deprivation was confirmed by histologic evidence of neuronal atrophy and apparent cell loss in sections of the superior cervical ganglia (SCG) and by marked decreases (65-80%) of SCG neurotransmitter-synthesizing enzyme activity levels. By using the autoimmune approach a new source of guinea pigs was found which consistently produced high titers of cross-reacting anti-NGF antibodies. Experiments were designed to examine the response of the sensory neuron to injury while chronically deprived of NGF. Total neuronal counts in the sixth lumbar DRG 98 days after sciatic nerve crush showed no difference between NGF-deprived and control ganglia. Measurement of the size spectrum of DRG neurons showed evidence of atrophy of the NGF-deprived neurons in both the uninjured and axotomized side compared to respective controls. The mean volume of uninjured sensory neurons measured in the NGF-deprived guinea pigs was decreased 27.7% (P less than .05) compared with that of control guinea pigs. The degree of regeneration 6 days following a nerve crush was the same in NGF-deprived sensory neurons and in controls when measured by the "pinch test" and by isotope-labeled axonal transport studies.(ABSTRACT TRUNCATED AT 250 WORDS)