65 bipolar patients who had shown a complete response to lithium prophylaxis over a 5-year period were followed up for a further period of 5 years. 12.7% of them had at least two affective episodes during the latter period, despite persistently adequate compliance. These late non-responders, as compared with stable responders, had a significantly higher number of previous affective episodes and hospitalizations and a significantly longer duration of illness. It is suggested that the main determinant of late non-response is the 'driving force' of the illness, finally overwhelming the prophylactic effect of lithium.