We aimed to explore key themes for the implementation of guidelines' prescribing recommendations. We interviewed a purposeful sample of 25 participants in British primary care in late 2000 and early 2001. Thirteen were academics in primary care and 12 were non-academic GPs. We asked about implementation of guidelines for five conditions (asthma, coronary heart disease prevention, depression, epilepsy, menorrhagia) ensuring variation in complexity, role of prescribing in patient management, GP role in prescribing and GP awareness of guidelines. We used the Theory of Planned Behaviour to design the study and the framework method for the analysis. Seven themes explain implementation of prescribing recommendations in primary care: credibility of content, credibility of source, presentation, influential people, organisational factors, disease characteristics, and dissemination strategy. Change in recommendations may hinder implementation. This is important since the development of evidence-based guidelines requires change in recommendations. Practitioners do not have a universal view or a common understanding of valid 'evidence'. Credibility is improved if national bodies develop primary care guidelines with less input from secondary care and industry, and with simple and systematic presentation. Dissemination should target GPs' perceived needs, improve ownership and get things right in the first implementation attempt. Enforcement strategies should not be used routinely. GPs were critical of guidelines' development, relevance and implementation. Guidelines should be clear about changes they propose. Future studies should quantify the relationship between evidence base of recommendations and implementation, and between change in recommendations and implementation. Small but important costs and side effects of implementing guidelines should be measured in evaluative studies.