AbstractTo ascertain whether the development of dendritic cells (DC) in mouse lymphoid organs is dependent on granulocyte/macrophage colony‐stimulating factor (GM‐CSF), we determined the number of DC in the thymus, spleen and lymph nodes of normal mice, of mice with the genes coding for GM‐CSF or its receptor inactivated, and of transgenic mice with excessive levels of GM‐CSF. DC were extracted from the tissues and enriched prior to flow cytometric analysis. The total DC level and the incidence of DC expressing lymphoid‐related markers (CD8hiCD11blo) and myeloid‐related markers (CD8loCD11bhi) were monitored. Both in GM‐CSF null mice, and GM‐CSF receptor null mice, DC of all surface phenotypes were present in all lymphoid organs; only small decreases in DC levels were recorded, except for the lymph nodes of GM‐CSF receptor null mice which showed a more pronounced (threefold) decrease in DC numbers. Since the GM‐CSF receptor null mice lacked the β chain common to the GM‐CSF, interleukin (IL)‐3 and IL‐5 receptors, the development of DC in the absence of GM‐CSF was not due to common β chain mediated developmental signals elicited by IL‐3 or IL‐5. In GM‐CSF transgenic mice, there was only a 50 % increase in DC numbers in thymus and spleen, paralleling an increase in overall cellularity, but a more pronounced (threefold) increase in DC numbers in lymph nodes. There was no evidence that GM‐CSF had a selective effect on any particular DC subpopulation defined by CD8 or CD11b expression. We conclude that the development of most lymphoid tissue DC can proceed in the absence of GM‐CSF, although this cytokine can produce some elevation of DC levels. It is not clear whether the enhancing effect of GM‐CSF is direct or an in