D5 is a low-molecular-weight cyclic siloxane used for industrial and consumer product applications. The objective of the present study was to assess potential toxic and immunomodulatory consequences of inhalation exposure to D5. Male and female Fischer 344 rats (25/group) were exposed by whole body inhalation to 0, 10, 25, 75, or 160 ppm D5 6 h/day, 7 days/week for 28 days. Clinical signs, body weights, and food consumption were recorded. On the day following the final exposure, 10 rats/group/sex were euthanized and a complete necropsy performed. Following a 14-day nonexposure recovery period, the remaining 5 rats/sex/group were necropsied. Body and organ weights were obtained and a complete set of tissues was taken for histopathology. Samples were also collected for serum chemistry, hematology, and urinalysis. Immunotoxicology-designated rats (10/sex/group) were immunized with sheep erythrocytes (sRBC) 4 days prior to euthanasia and cyclophosphamide (CYP) was administered i.p. to positive controls on days 24 through 28. The anti-sRBC antibody-forming cell (AFC) response was evaluated in a standard plaque assay. Blood was also collected for examination in the anti-sRBC enzyme-linked immunosorbant assay (ELISA). D5 exposure did not modulate humoral immunity, while the internal control, CYP, produced the expected suppression of the AFC response. D5 exposure caused no adverse effects on body weight, food consumption, or urinalysis parameters. Serum alkaline phosphatase (SAP) was significantly decreased in females at terminal (12%, 160 ppm) and recovery sacrifice. A significant increase in the liver-to-body weight ratio was observed in female animals at the end of exposures (13%, 160 ppm), but was not noted in recovery animals from the same exposure group. In males, significant increases in liver-to-body weight (5%) and thymus-to-body weight (14%) ratios were also noted at the high dose at terminal sacrifice and were not present at recovery. At recovery only, a significant increase in spleen-to-body weight ratios (14 and 17%; 25 and 160 ppm, respectively) was noted. At the end of exposure, histopathological analysis indicated an increased incidence and severity of nasal (Level 1) goblet cell proliferation. Focal macrophage accumulation in the lung was also observed to be increased in incidence in both sexes at 160 ppm. At the end of the recovery period, the effects in both of these organs appeared to be reversible. In summary, D5 inhalation exposure did not alter humoral immunity and caused only minor, transient changes in hematological, serum chemistry, and organ weight values. Histopathological changes were confined to the respiratory tract and appeared to be reversible. The no observed effect level for systemic toxicity, based primarily on the liver weight changes, was 75 ppm.