The clinical immune response of cattle experimentally challenged with bovine herpesvirus 1 (BHV-1) after treatment with florfenicol at the time of BHV-1 vaccination, was measured in groups of 10 unvaccinated beef-type, crossbred steers randomly assigned to one of 4 treatment groups: (a) florfenicol-treated and BHV-1-vaccinated (FF+, VX+), (b) florfenicol-untreated and BHV-1 vaccinated (FF-, VX+), (c) florfenicol-treated and BHV-1 unvaccinated (FF+, VX-), and (d) florfenicol-untreated and BHV-1 unvaccinated (FF-, VX-). Recommended doses of florfenicol were given on days 24 and 22 before challenge. BHV-1 vaccine was administered both intranasally and i.m. on day 22 before challenge to cattle in both vaccinated groups. BHV-1 experimental challenge was done 21 days after vaccination (day 0). Post-challenge rectal temperature was significantly lower in vaccinated groups (FF+, VX+ and FF-, VX+) as compared to unvaccinated groups (FF+, VX- and FF-, VX-). Post-challenge cumulative clinical score composed of cough, nasal and ocular discharge, and respiration character, was significantly lower in vaccinated groups (FF+, VX+ and FF-, VX+), as compared to unvaccinated groups (FF+, VX- and FF-, VX-). Post-challenge BHV-1 shedding was significantly reduced in vaccinated groups (FF+, VX+ and FF-, VX+) as compared to unvaccinated groups (FF+, VX- and FF-, VX-). Rectal temperature and clinical illness scores following vaccination and challenge were not different between florfenicol-treated (FF+, VX+ and FF+, VX-) and non-treated cattle (FF-, VX+ and FF-, VX-). Serum neutralization titres were significantly greater in florfenicol-treated groups (FF+, VX+ and FF+, VX-) as compared to untreated groups (FF-, VX+ and FF-, VX-) 21 days after vaccination (day 0). Leukograms were within normal limits for all treatment groups at all time points. Vaccinated calves (FF+, VX+ and FF-, VX+) lost 7.95 lb/head, while unvaccinated calves (FF+, VX-, and FF-, VX-) gained 3.15 lbs/head day -24 to day -20. It is concluded that BHV-1 vaccinated calves developed clinically protective immune responses. There was no indication of interference by florfenicol with response to vaccination.