We have developed methods for the isolation, cultivation, and investigation of human uveal melanocytes (UM). Uveal melanocytes grow well and produce melanin in vitro in the presence of basic fibroblast growth factor (bFGF), cyclic adenosine monophosphate-elevating agents, and serum. Cultured UM respond to various factors. Certain growth factors (bFGF and hepatocyte growth factor, etc.), endothelin, adrenergic β2-receptor agonists, and some prostaglandins (EP2-receptor agonists and certain TP-receptor agonists) stimulate, while transforming growth factor-β2, interleukin-6, and cholinergic agonists inhibit melanogenesis and/or growth of UM in vitro. α-Melanocyte-stimulating hormone, adrenocorticotropic hormone, various sex hormones, and prostaglandin F2α showed no effect on the growth and melanogenesis of cultured UM. The stability of UM in vivo may be controlled by these factors. Disturbance of this balance may lead to certain rare pathologic pigmentary changes of the iris. UM are relatively stable in vivo; they usually do not respond (proliferate or show dynamic changes in melanogenesis) to various environmental factors. The differences of the in vivo behavior between uveal and epidermal melanocytes may be determined by both cellular factors and environmental factors.