Intermittent sunburns, particularly in childhood, are the strongest environmental risk factor for malignant melanoma (MM). In mice, a single neonatal ultraviolet radiation (UVR) exposure induces MM whereas chronic doses to adult mice do not. Neonatal UVR alters melanocyte migration dynamics by inducing their movement upwards out of hair follicles into the epidermis. UVR is known to induce inflammation and recruitment of macrophages into the skin. In this study we have used a liposomal clodronate strategy to deplete macrophages at the time of neonatal UVR, and shown functionally that this reduces the melanocyte proliferative response. This effect was not reproduced by depletion of CD11c-expressing populations of dendritic cells. Based on epidermal expression array data at various time points after UVR, we selected mouse strains defective in various aspects of macrophage recruitment, activation and effector functions and measured their melanocyte UVR response. We identified Ly6c(low)MHCII(hi) macrophages as the major population promoting the melanocyte response across multiple strains. The activity of this subpopulation was CCR2-independent and partly IL17-dependent. By helping induce this effect, the infiltration of specific macrophage subpopulations after sunburn may be a factor in increasing the risk of subsequent neoplastic transformation of melanocytes.Journal of Investigative Dermatology accepted article preview online, 15 January 2013; doi:10.1038/jid.2013.9.