Morphometric methods were used to study the nucleolar ultrastructure during the development of human blood monocytes into macrophages in suspension culture. Nucleolar volume (Vn), surface area (Sn), volume fraction within the nucleus (Vvn), surface-to-volume ratio [(S/V)n] and number of nucleolar profiles per section were measured in 20 healthy adults over a 6-day period, and the results examined using multivariate and univariate analyses of variance. Highly significant increases in Vn Sn and^vn occurred with no significant change in the number of nucleolar profiles per section; (S/V)n decreased during culture; no significant differences were found between male and female subjects. These nucleolar changes would be consistent with an increased protein synthesis during macrophage development. The results provide quantitative data against which changes in nucleolar morphology during macrophage development in disease states may be assessed.