National factor(s) influencing publication output in the highest ranked medical journals are largely unknown. We sought to examine the relationship between national research funding and English proficiency on publication output. We identified all original research articles appearing in the five highest ranked general medical journals between 1997 and 2001. Using the country of the corresponding author as the source nation for each article, we determined a standardized publication rate across developed nations. We used multiple regression techniques to determine the influence of national expenditures on research and scores from the Test of English as a Foreign Language (TOEFL), a surrogate for English proficiency, on publication output. There was a significant relationship of national spending on research and TOEFL scores to publication output of developed countries (p = 0.04; p < 0.01, respectively). These two variables explained approximately 71.5% of the variation in publication rate across developed nations around the world (R = 0.85; p < 0.01). Normalized for population size, English-speaking nations and certain northern European countries such as Denmark, The Netherlands, Switzerland, and Sweden had the highest rate of publication in the five highest ranked general medical journals, while Asian countries had generally low rates of publication. Research spending and English proficiency were strongly associated with publication output in the highest ranked general medical journals. While these data cannot be considered definitive due to their observational nature, they do suggest that for English-language medical journals, research funding and English proficiency may be important determinants of publication.