OBJECTIVE To evaluate use of the virulence-associated protein of Rhodococcus equi in immunizing foals against R equi pneumonia. METHODS Eight (experimental group) and 6 (controls) mares with their foals. METHODS Virulence-associated protein extracted from R equi was used to prepare an acetone-precipitated. Triton X-extracted (APTX) antigen. After determination of the efficacy of passive immunization, in untreated foals or in foals given plasma from a horse vaccinated with APTX antigen or from a nonvaccinated horse, a field trial was done to evaluate the efficacy of vaccination of 8 mares, twice with APTX before parturition, and of their foals at ages 3 and 5 weeks; 6 mares and their foals served as unvaccinated controls. All 2-day-old foals were given plasma from local donor horses inoculated with a locally produced bacterin. Serum opsonizing activity produced by vaccination with APTX was determined. Passively immunized foals were challenge exposed with an aerosol of virulent R equi. Foals of the field trial were exposed to enzootic R equi infection. RESULTS Inoculation with APTX resulted in high IgG antibody liters with opsonizing activity. Passive immunization of foals with plasma from an immunized horse enhanced bacterial clearance from the lungs, compared with that in foals not given plasma or given plasma without APTX antibodies. Vaccination of mares and foals exposed to natural infection resulted in development of R equi pneumonia in 4 of 8 vaccinated foals, but in only 1 of 6 unvaccinated foals. CONCLUSIONS Vaccination with APTX antigen led to high-titer, opsonizing antibody. Plasma from a vaccinated horse appeared to enhance clearance of R equi from the lungs of foals. Paradoxically, vaccination of mares and their foals with APTX antigen did not protect foals and may have enhanced R equi pneumonia in the foals.