OBJECTIVE To explore the discomfort experienced by general practitioners in relation to decisions about whether or not to prescribe. DESIGN Focused interviews of general practitioners about prescribing decisions that made them uncomfortable. Analysis based on the critical incident technique. SETTING One family practitioner committee area in the north of England. RESPONDENTS 69 principals and five trainee general practitioners. MAIN OUTCOME MEASURES Drugs and clinical problems associated with prescribing discomfort. Reasons given by doctors for making the prescribing decisions they did and reasons for feeling uncomfortable. RESULTS Antibiotics, tranquillisers, hypnotics, and symptomatic remedies were most often associated with discomfort, but any prescribable item could be associated with discomfort. Respiratory diseases, musculoskeletal problems, and anxiety were most often associated with discomfort, but again any condition could be associated. The main reasons given for the decisions made were patient expectation, clinical appropriateness, factors related to the doctor-patient relationship, and precedents. The main reasons given for feeling uncomfortable were concern about drug toxicity, failure to live up to the general practitioner's own expectations, concern about the appropriateness of treatment, and ignorance or uncertainty. CONCLUSIONS Many considerations, including medical, social, and logistic ones, influence the decision to prescribe in general practice. The final action taken depends on a complex interaction of these disparate influences.