Alloxan damages insulin-producing cells and has been used as an inducer of experimental diabetes in several animal species. In this study, administration of alloxan (40 mg/kg, i.v.) to rats was followed by a selective and time-dependent reduction in the number of pleural mast cells (50 +/- 2.2%, p < 0.01; mean +/- SEM), while mononuclear cell and eosinophil counts were not altered. As compared to naive rats, the reduction in mast cell numbers was first noted 48 h following alloxan administration and remained unaltered for at least 60 days. It is noteworthy, that the depletion in the mast cell population was not accompanied by alterations in the total amount of histamine stored per cell. Sensitized rats turned diabetic by alloxan treatment performed 72 h before challenge showed a less pronounced antigen-induced mast cell degranulation compared to nondiabetic rats. Moreover, rats injected with alloxan 72 and 48 but not 24 h before challenge, reacted to allergenic challenge with 50% reduction in the number of eosinophils recruited to the pleural cavity within 24 h. We found that the less pronounced eosinophil accumulation did not relate to an intrinsic cell locomotor abnormality since eosinophils from diabetic rats presented similar chemotactic responses to LTB4 and PAF in vitro as compared to matching controls. Insulin (3 IU/rat) restored basal levels of mast cells and reversed the subsequent inhibition of allergen-induced pleural eosinophilia, suggesting a causative relationship between these phenomena. Treatment with insulin also significantly increased the number of mast cells in the pleural cavity of naive rats (from 637 +/- 57 to 978 +/- 79 x 10(3) cells/cavity, p < 0.001). Consistently, previous depletion of mast cells by means of local treatment with compound 48/80 significantly reduced the antigen-induced eosinophil recruitment in sensitized animals. We conclude that the reduction in the pleural mast cell population noted in alloxan-treated rats could be directly implicated in the diminished pleural eosinophil influx following allergen challenge. This hyporesponsiveness is independent of an intrinsic abnormality of cell chemotaxis, but can be imitated by local mast cell depletion.