Objective: To compare the demographics of general practitioners in two practice-based research networks (PBRNs) and to explore the generalisability of research findings from these PBRNs. Design, setting and participants: Cross-sectional questionnaire-based study of two geographically-based PBRNs - Hunter New England Central Coast Network of Research General Practices (NRGP) and Primary Healthcare Research Network-General Practice (PHReNet-GP) - during August-September 2010. All 183 GP members of both PBRNs were invited to participate; of these, 140 (77%) participated. Main outcome measures: GPs' demographics, use of languages other than English in consultations, and previous participation in research. Practices' use of practice nurses. Socioeconomic status and rurality or urbanicity of practice location. Results: Compared with PHReNet-GP GPs, NRGP GPs were more likely to work in a practice employing a practice nurse (100% v 53.8%; 95% CI for difference, 30.5%-61.8%; P < 0.001), worked in larger practices (2.9 more full-time-equivalent GPs per practice; 95% CI, 2.1-3.6; P< 0.001), and were less likely to work in a major city (33.7% v 89.7%; 95% CI for difference, 42.8%-69.3%; P< 0.001). NRGP GPs also worked in practices with a different spectrum of socioeconomic disadvantage, and were less likely to have been involved in research as a researcher (35.4% v 76.9%; 95% CI for difference, 25.3%-57.8%; P< 0.001). Fewer NRGP GPs consulted in languages other than English (8.9% v 64.1%; 95% CI for difference, 39.1%-71.2%; P< 0.001). There were also differences between these and national general practice statistics. Conclusions: These results suggest possible lack of generalisability of findings from some types of studies conducted in single PBRNs. In such circumstances, collaboration of PBRNs may produce more generalisable results.