Gastric mucosal lymphocyte subpopulations were determined by an indirect immunoperoxidase method applied to cryostat sections of gastric biopsies obtained from 12 patients with pernicious anemia (PA group) and from 12 patients whose stomachs were endoscopically and histologically normal (comparison group). T-Cell populations were identified by means of monoclonal antibodies directed against all T cells (UCHT1), T suppressor cells (anti-Leu-2a), and T helper cells (anti-Leu-3a). Non-T cell numbers were estimated indirectly. Concentrations of all T cells, T suppressor cells, T helper cells, and non-T cells were all significantly greater in the PA than in the comparison group. The most striking difference was in non-T cell numbers, which showed an approximately sixfold increase in the PA group. Mean T/non-T cell ratios in PA and comparison groups were significantly different (0.49 and 1.50, respectively). T suppressor/T helper cell ratios were similar in the two groups. There were highly significant positive correlations between numbers of non-T and T helper cells, and non-T and T suppressor cells in PA, but not in comparison groups. If, as seems likely, the majority of non-T cells in these gastritic stomachs were in fact cells of B lineage, these results would be consistent with the hypothesis that gastric mucosal damage in pernicious anemia is mediated primarily by a humoral mechanism, which may involve cytotoxic autoantibodies.