Hyperlactaemia was induced by means of a standard exercise test in 10 diabetics receiving normal treatment with biguanides (either buformin, metformin, or phenformin) in combination with either a sulfonylurea or insulin. The treatment regimen was then continued without biguanides for 3 weeks and the exercise test was repeated at the end of this period. All 3 biguanide preparations induce hyperlactaemia in diabetics. Physical stress leads to an additional increase in lactate, which reaches pathological proportions. Discontinuation of biguanide treatment leads to a significant decrease in resting and stress values. In a comparison of the 3 biguanide products, phenformin induced significantly higher lactate values in response to exercise than buformin. Of the biguanides, phenformin appears to carry the greatest risk of causing hyperlactaemia in susceptible patients, induced by concurrent circumstances, with progression to severe lacticate acidosis. The special pharmacokinetic properties of phenformin and the 8-fold higher incidence of lacticate acidosis than under buformin or metformin therapy support this observation.