Twenty-four-hour ambulatory electrocardiographic monitoring was used to determine the incidence of arrhythmia while on-call and its relationship to stress and fatigue in 20 healthy medical interns. Mitral valve prolapse was present in 8 of 19 interns (42%). Heart rates ranged from a maximum of 103-167 beats/min (135 +/- 16) to a minimum of 38-61 beats/min (47 +/- 5). Interns had at least one episode of sinus tachycardia/h during 57% +/- 21% (range, 8-88%) of their hours on-call. Atrial premature beats (APB) were present in 19 of 20 (95%) and ventricular premature beats (VPB) in 12 of 20 (60%) subjects. APB/h ranged from 0 to 1.2 (0.4 +/- 0.3) and VPB/h from 0 to 23 (2 +/- 6). Three interns had multiform VPB and two had ventricular couplets. More APB/h occurred in interns under greater stress (0.5 +/- 0.4/h vs 0.3 +/- 0.1/h, p < 0.05) and combined stress and fatigue (0.6 +/- 0.4/h vs 0.2 +/- 0.2/h, p < 0.01). More VPB/h (5 +/- 9/h vs 0.5 +/- 0.6/h, p < 0.05) and higher (Lown) grade ventricular ectopy (2.3 +/- 1.6 vs 0.8 +/- 1.1; p < 0.05) occurred in interns under greater combined stress and fatigue. Mitral valve prolapse, sleep deprivation and caffeine intake were not associated with increased arrhythmia. The authors conclude that (1) rapid sinus tachycardia is frequent in interns while on-call and (2) interns experiencing greater stress and fatigue have more APB/h, VPB/h, and higher grade ventricular ectopy. These data support the notion that stress and fatigue may contribute to arrhythmia in healthy normal subjects.