A small, but clinically significant proportion of acne patients fail to respond adequately to antibiotic therapy. All non-responding acne patients attending the Leeds General Infirmary between September 1985 and April 1986 (49 out of a total of 610 patients; 8%) were investigated with respect to changes in their acne grade, microbial flora and sebum excretion rate. They were compared with 22 age and sex matched untreated control subjects. It was found that in 65% of non-responding patients there was no microbiological abnormality, in 16% there was evidence of Gram-negative folliculitis and 20% carried predominantly antibiotic resistant propionibacteria compared with only 5% of untreated controls. There was a significant association between erythromycin therapy and the isolation of erythromycin resistant propionibacteria (P less than 0.001). A causal link, however, has yet to be established between carriage of antibiotic resistant propionibacteria and failure to respond to antibiotic therapy. Our results show that for most patients with recalcitrant acne a non-microbiological explanation must be sought for the lack of therapeutic success. The mean sebum excretion rate (SER) of the non-responding patients was significantly higher than that of matched untreated acne patients (P less than 0.001). A majority of non-responders (69%) had an SER above the upper 95% confidence limit of the control mean. The SER may affect treatment efficacy by influencing the antibiotic concentration within the pilosebaceous ducts.