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Background: Non-participation of General Practitioners (GPs) hampers primary care research. Using existing network structures can improve participation, but may introduce sampling effects., Objectives: To examine the role of network-based recruitment and other determinants of participation, and to estimate effects of sampling and non-participation on generalizability., Methods: For a study of quality of care assessment, we recruited GPs from a regionally defined population and a GP network. Effects of sampling and non-participation were analysed by comparing characteristics between participants, target samples, and reference data for all German GPs. Factors influencing study participation were assessed in multiple logistic regression., Results: Compared to the regional sample, network GPs were more likely to complete survey questionnaires (92% versus 69%) and to participate in the study (66% versus 23%). Compared to national reference data, study participants from both populations were younger, had a higher level of professional training, and included more men. These differences were already present in the network target sample, but were largely attributable to selective participation in the regional sample. Network membership remained the strongest determinant of participation in multiple logistic regression (odds ratio 5.01; 95% confidence interval 2.53-9.91). A younger age, higher professional training, and membership in the German Society of General Practice were also predictive of participation., Conclusions: Although network-based recruitment of GPs increases participation rates, sample effects are similar in size and direction as effects of non-participation in the regionally defined population. Careful analysis of participants based on publicly available data is therefore crucial for the assessment of generalizability.