Human malignant melanoma can form tumor colonies in soft agar, and at least two major morphological variants can be identified. Host cells play an important role in human melanoma colony formation, and their effects on the colony variants are selective. Neuroendocrine compounds also modulate expression of the melanoma TCFU pigmentary variants. This system appears suitable for evaluation of the response of melanoma TCFUs to chemotherapy, retinoids, heat, and radiation.