Multiple brief periods of rapid ventricular pacing confer both short- and long-term protection on the ischaemic heart. The duration of the short-term protection does not exceed 2 h, whereas the long-term protective effect appears several hours after the inducing insults, with maximal protection 24-48 h later. Up to now, delayed cardiac protection by preceding ischaemic insults against harmful consequences of stress has been produced in the normal, healthy animal only. The purpose of this study was, therefore, to test whether delayed cardiac protection can be induced in experimental atherosclerosis in rabbits produced by feeding cholesterol-rich diet over 2 months. Repeated brief periods of rapid ventricular pacing were used to induce delayed protection of the heart. Moderation of post-pacing right intracavitary ST segment elevation and that of the left ventricular end-diastolic pressure (both produced by ventricular overpacing: 500 beats/min for 15 min) were found in normal animals as well as in those fed cholesterol-enriched diet. The short-lived protection induced by a single 'preconditioning' pacing was reproducible only in normal animals. As measured by means of radioimmunoassay, the protective effect of either short- or long-term protection appeared in parallel with an attenuation of ischaemia-induced increase in cardiac cyclic AMP content, in both normal and atherosclerotic rabbits. An increase in cardiac cyclic GMP content was characteristic of the short- but not long-term protection. These results suggest that the delayed cardiac protection by preceding multiple brief rapid pacings operates even in experimental atherosclerosis, but the short-term protection induced by a single preconditioning stimulus is lost.