In order to determine the mast cell requirements in murine delayed-type hypersensitivity (DTH), the effects of the antihistamine chlorpheniramine, the inhibitor of mast cell degranulation repirinast (CAS 73080-51-0, MY-5116), the lipoxygenase and cyclooxygenase inhibitor BW-755C (3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline), and the cyclooxygenase inhibitors ibuprofen, diclofenac and phenylbutazone on murine DTH reactions were examined. When chlorpheniramine (50 mg/kg) was administered orally immediately after, 5 h, or 9 h after antigen challenge, it did not show any effect on sheep red blood cells (SRBC)-induced delayed footpad reaction (FPR) in mice. On the other hand, when chlorpheniramine was administered orally 16 h after antigen challenge, it significantly inhibited SRBC-induced delayed FPR (p < 0.01). When repirinast (30, 100 mg/ kg) was administered orally 16 h after antigen challenge, it significantly inhibited delayed FPR in a dose-dependent manner. BW-755C (50 mg/kg) showed no significant effect on delayed FPR when it was administered 1 h, 7 h, or 13 h after challenge. However, it significantly inhibited delayed FPR when it was administered 16 h after antigen challenge (p < 0.01). Ibuprofen, diclofenac, or phenylbutazone showed no significant effect on delayed FPR even if it was administered 16 h after antigen challenge. These results demonstrate that mast cells could be involved in DTH reactions and that histamine and leukotrienes may play an important role in DTH reactions in mice.