Over 10 million workers in the United States are exposed to metal working fluids (MWFs) through dermal contact and/or inhalation of aerosolized fluids. The objective of this study was to elucidate the response of skin to dermal exposure to MWFs. Four-to six-week-old B6C3F1 mice of both sexes were divided into eight groups (n=5/group) and exposed to 200 μ1 of 0%, 5% (pH 7 and 9.7) and 100% (pH 10.4), unused MWFs/H2O by topical application to the unshaven back (cervical to sacral region), twice a week for 6 weeks. Skin-mast cell number in females of most treated groups and of two male groups (100% and 5%, pH 7) were significantly higher than the control groups. Eventhough both males and females (treated with 100% MWF/H2O) showed an increase in the skin-histamine levels (38% and 41%, respectively), this increase was significant in females only (ANOVA, P≤0.05). Dermal exposure to 100% MWFs increased liver weight significantly in both sexes. Ulcers and associated inflammation were seen in the skin of mice treated with 100% unused MWFs and sacrificed at 6 weeks, but not in the recovery groups. Hypertrophy of the sebaceous gland epithelium is present in all mice treated for 6 weeks and sacrificed immediately. However, only the mice treated with 100% MWF retained the hypertrophy of this epithelium after a 6-week recovery period. In conclusion, dermal exposure to unused semi-synthetic MWF penetrates the normal skin, induces mast cell accumulation in the skin, produces hypertrophy of the sebaceous glands, and may affect females more than males.