The objective of this study was to assess whether geographic differences in antibiotic-prescribing rates for patients with pharyngitis could be explained by intersite differences in patients' clinical characteristics and in how physicians responded to these clinical cues when making decisions. As part of the initial phase of a prospective controlled trial to improve physicians' diagnostic ability, the authors enrolled cohorts of consecutive patients seen at staff-model--HMO student health services in Pennsylvania and Nebraska. Physicians' decisions whether to prescribe antibiotics for 310 consecutive patients presenting with pharyngitis to the former and 214 such patients presenting to the latter at the time of the initial visit were examined. There was a large discrepancy between the antibiotic-prescribing rates at the student health services in Pennsylvania, 106/310, 32.4%, and Nebraska, 156/214, 72.9%. The clinical variables significantly independently associated with treatment at both sites in a logistic regression model were fever, adjusted odds ratio = 2.1 (95% CI = 1.1, 3.8); exudates, 5.4 (2.8, 10); palatine petechiae, 6.5 (1.5, 28); rhinorrhea, 0.46, (0.25, 0.85); and high risk of complications, 3.8 (1.04, 14). There was a significant interaction between site and anterior cervical adenopathy, 5.5 (1.6, 19); and a borderline interaction between site and rhinorrhea, 2.4 (0.89, 6.7). Site was not a significant independent predictor of treatment, 1.8 (0.45, 6.6.). Practice variation was related to geographic differences in patients' clinical characteristics and in how physicians responded to these factors when prescribing antibiotics. How physicians weight patients' clinical characteristics when making decisions may be an important element of their "practice styles."