Patients with peripheral arterial disease (PAD) and intermittent claudication often have coronary artery disease (CAD) and other comorbid medical problems. There is a paucity of information on the impact of coexistent medical conditions on exercise capacity and functional status in patients with PAD. This study examined the impact of CAD, diabetes, cigarette smoking, prior peripheral surgical revascularization and other medical conditions on claudication pain times and peak oxygen capacity (VO2) during maximal effort treadmill testing in 119 male outpatient volunteers (ankle-brachial index (ABI) of 0.65 +/- 0.2, mean +/- SEM) with a history of Fontaine Stage II PAD. Smoking status was significantly related to ambulatory function. Current smokers had a lower peak VO2 expressed in l/min than either former or never smokers (ANCOVA adjusted for age, p = 0.003). However, after adjustment for body weight, there was only a trend for a difference in peak VO2 between current (13.2 +/- 0.5 ml/kg per min), former (14.2 +/- 0.4 ml/kg per min) and never (15.4 +/- 1.0 ml/kg per min) smokers (ANCOVA, p = 0.10). Current smokers had a shorter time to onset of claudication pain (p = 0.023) and shorter maximal claudication pain times (p = 0.029) than former or never smokers (p = 0.023). The ABI 1 min after cessation of exercise was also lower in smokers compared to former and never smokers (p = 0.018). There were no significant differences in functional performance measures or time to recovery from maximal claudication pain when patients were categorized on the presence or absence of CAD, diabetes, peripheral revascularization, arthritis, hypertension or dyslipidemia. Therefore, smoking adversely affected exercise capacity in these PAD patients, whereas the presence of CAD, diabetes and other medical problems had a relatively minor impact on exercise capacity. In conclusion, the relatively minor impact of comorbid medical conditions on walking ability in patients with PAD reflects the overwhelming limitation in ambulatory function due to the claudication pain.