OBJECTIVES--To see whether autonomic regulatory mechanisms play a part in transient myocardial ischaemia in patients treated with beta blockers. DESIGN--Prospective study. SETTING--Outpatients' clinic. PATIENTS--51 consecutive patients with angiographically documented coronary artery disease, stable angina, and transient myocardial ischaemia despite beta blockade. INTERVENTIONS--24 hour ambulatory electrocardiographic monitoring for analysis of variability in ST depression and heart rate. MAIN OUTCOME MEASURES--Numbers of episodes of ischaemia, with an ST depression of > or = 0.1 mV 80 ms after the J point that lasted > or = 60 s at an interval of > or = 60 s from a previous ischaemic episode. Heart rate at onset of ischaemia. Normalised spectral analysis of heart rate variability; ratio of low to high frequency power to assess the sympathovagal balance. RESULTS--Despite treatment, 258 episodes of transient ischaemia were recorded. At heart rates at onset of ischaemia of < 70 beats per minute a high ratio of low to high frequency power accompanied the ischaemic events and was paralleled by a remarkably reduced high frequency power. The high ratio--that is, enhanced sympathetic tone during ischaemia--was mainly found in the early morning. By contrast, ischaemic episodes with heart rates at onset of > or = 70 beats per minute were not associated with significant changes in the parameters of autonomic function. CONCLUSIONS--During beta blockade the residual transient ischaemia is associated with decreased variability in heart rate. In particular, in ischaemic episodes with a low heart rate at onset the neural regulation of the heart plays a part. Apparently, variability in heart rate is not sufficiently modified by beta blockers to prevent all ischaemia. The ischaemia related change in the autonomic nervous system during the early morning is in agreement with previous studies, showing increased cardiovascular risk at this time of the day.