During the fall of 1991 and 1992, a study of bovine respiratory disease (BRD) was carried out at a commercial feedlot in south-western Ontario. The purpose of the study was to: (1) evaluate two antimicrobials based on treatment and mortality rates, days to treatment and average daily gain; (2) compare the efficacy of two differing times of mass medication administration and (3) determine if changes in the nasopharyngeal bacterial pathogen population in calves occurred. Six hundred auction market calves averaging 200 kg arrival weight were placed in pens often, within two differing prophylactic strategy groups and a control group. Within the pens receiving prophylaxis, calves were randomly administered tilmicosin or oxytetracycline. Treated and untreated calves were sampled and cultured for nasopharyngeal pathogen growth at arrival, time of clinical treatment and 28 days post arrival. Treatment rates differed significantly from each other (p < 0.05), with BRD treatment rates of 37.5%, 18.1% and 8.3% for control, oxytetracycline and tilmicosin mass medicated calves, respectively. Both prophylactic antimicrobials decreased mortality significantly compared to controls receiving no prophylaxis. Improved feed conversion in arrival mass medicated pens was statistically significant in the second year of the trial, compared to control pens. P. haemolytica represented 91.0% of all bacterial isolates at the time of arrival, and 86.6% at the time of clinical treatment, but decreased to 19.4% at twenty-eight days post arrival. The nasopharyngeal bacteria isolated and P. haemolytica resistance patterns changed over time, but did not appear to be affected significantly by the prophylactic antimicrobial employed. Antimicrobial resistance in P. haemolytica isolates was more common against oxytetracycline than tilmicosin. Concurrent oxytetracycline, penicillin and ampicillin resistance in P. haemolytica isolates was more common than expected by chance alone. P. haemolytica serotype 1 represented 78.5% of all identified serotypes. Antimicrobial resistance in serotype 1 isolates was significantly higher than in all other serotypes combined. Based on this study we concluded that tilmicosin significantly decreased treatment rates and BRD associated costs compared to oxytetracycline. Statistically significant ADG differences found in the early feeding period did not persist beyond 56 days on feed. Arrival prophylaxis significantly improved feed conversion, compared to control pens.