Objective - To determine the effects of dexamethasone on development of IgG subclass responses following vaccination of healthy horses. Animals - 11 mature Thoroughbreds. Procedure - Horses received 2 IM injections at 2-week intervals of a vaccine containing inactivated infectious bovine rhinotracheitis, bovine viral diarrhea, and parainfluenza-3 viral antigens and were then randomly assigned to 2 groups. Six horses received dexamethasone (0.2 mg/kg of body weight, IM) twice weekly for 8 weeks starting the day of the first vaccination. Five control horses received an equivalent volume of saline (0.9% NaCI) solution. Antigen-specific serum IgG subclass titers were determined weekly after vaccination by use of an ELISA. Results - Vaccination resulted in similar antigen-specific serum IgG(T) titers in dexamethasone-treated and control horses. In contrast, although control horses developed IgGa and IgGb responses after vaccination, corticosteroid administration completely inhibited these responses in treated horses. Conclusions and Clinical Relevance - Cortico steroids can have profound effects on primary immune responses in horses and can significantly affect IgG responses to inactivated vaccines. Corticosteroid treatment regimens commonly used to treat diseases in horses may result induction of a nonprotective IgG subclass response, leaving treated horses susceptible to disease. Additionally, mechanisms regulating IgGa and IgGb responses appear to differ from those regulating [gG(T) responses. Further defining these mechanisms is a critical step in designing effective vaccines, and corticosteroid-induced immunomodulation may be a valuable too[ for studying immune responses in horses.