Neuron loss occurs in the myenteric plexus of the aged rat. The myenteric plexus is composed of two mutually exclusive neuronal subpopulations expressing, respectively, nitrergic and cholinergic phenotypes. The goal of the present study, therefore, was to determine if neuron loss is specific to one phenotype, or occurs in both. Ad libitum fed virgin male Fischer 344 rats of 3 and 24 months of age were used in each of two neuronal staining protocols (n=10/age/neuron stain). The stomach, duodenum, jejunum, ileum, colon, and rectum were prepared as whole mounts and processed with either NADPHd or Cuprolinic Blue to stain, respectively, the nitrergic subpopulation or the entire population of myenteric neurons. Neuron numbers and sizes were determined for each preparation. Neuron counts from 24-month-old rats were corrected for changes in tissue area resulting from growth. There was no age-related loss of NADPHd-positive neurons for any of the regions sampled, whereas significant losses of Cuprolinic Blue-labeled neurons occurred in the small and large intestines of 24-month-old rats. At the two ages, the average neuron sizes were similar in the stomach and small intestine for both stains, but neurons in the large intestine were significantly larger at 24 months. In addition, numerous swollen NADPHd-positive axons were found in the large intestine at 24 months. These findings support the hypothesis that age-related cell loss in the small and large intestines occurs exclusively in the cholinergic subpopulation. It appears, however, from the somatic hypertrophy and the presence of swollen axons that the nitrergic neurons are not completely spared from the effects of age.