Herd size is frequently studied as a risk factor for swine diseases, yet the biological rationale for a reported association with herd size (whether positive or negative) is rarely adequately discussed in published epidemiological studies. Biologically plausible reasons for a positive association between herd size and disease include a greater risk of introduction of pathogens from outside the herd, greater risk of transmission of pathogens within and among herds when the herd is large, and effects of management and environmental factors that are related to herd size. However, compared with owners of small herds, owners of large herds might more frequently adopt management and housing practices that mitigate this theoretically increased risk. We used studies of pleuritis, pneumonia and pseudorabies to describe the epidemiological issues involved in evaluations of the relationship between management factors, herd size and disease. In future studies, we recommend that (i) herd size be measured in a way that best characterizes the true population at risk; (ii) studies that evaluate management-related risk factors should account for herd size wherever possible; (iii) population-based studies of the interrelationships among management factors and between management factors, herd size, herd density and pig density be done; (iv) likely biological reasons for any herd-size effect be postulated; and (v) the distribution of herd sizes in the source population and the study sample be described.