We hypothesized that skin fibroblasts from patients with neurofibromatosis (NF) may have abnormalities of growth in tissue culture to correlate with the clinical abnormalities of overgrowth and malignancy seen in this disease. Using five lines of NF cells, age- and passage-matched to normal controls, we found that NF fibroblasts grew more slowly and slopped growing at a lower population density than normal cells (P< 0.0005). The same cells also incorporated [3H] thymidine at a lower rate than normal skin fibrobasts (9,330 × 3,240versus42,100 × 6,840;P< 0.01), The addition of epidermal growth factor to the medium stimulated the growth of both the normal and the NF fibroblasts; however, the stimulation of the NF fibroblasts was inadequate to fully correct the slow growth rate (P< 0.025). NF cells (N= 5) were found to be morphologically different from normal skin fibroblasts (N= 5) in culture by light microscopy. NF cells were larger (approximately 9 x 104x 2 x 104versus2 x 104x 2 x 104A), pleomorphic, and failed to form confluent monolayers when growth ceased.