The purpose of this study is to determine the potential effects of octamethyIcyclotetrasitoxane (D4) on the immune system. The in-life phase for the studies was initiated April 19, 1994. The protocol was amended on May 16, 1995 to include repeat studies on those biological parameters which showed significant differences between D4-exposed groups and the control group. Two additional studies were included in the protocol via a note to file 11, dated April 12, 1996. These studies address the serum antibody response to sRBC on day 4 and day 6. This report encompasses 14 studies and consists of the development of a rat-based model for immunological assessment of test articles, the concurrent validationlevaluation of D4 for any potential immunological events, and studies directed at ascertaining if there was any vehicle dependence on dose. The departure from the classical mouse-based immunological assessment was prompted by the study sponsor in order to limit the mouse to rat extrapolations and to facilitate the comparison of other toxicological data generated for this compound in rats. In these D4 studies male and female Fischer 344 rats (10 per group) were used as the experimental animals. The route of administration was by oral gavage and the duration of exposure was daily for 28 days. Doses of D4 used were 10, 30, 100 and 300 mg/kg and were administered in com oil. The biological parameters were measured one day after the last exposure and immune cells were derived from blood and spleen. Blood for hematological studies and serum for antibody titers were collected by cardiac puncture. Rats, administered D4, showed a normal increase in body weight, with body weight change equivalent to the vehicle control group. There was a silght, but dose-dependent decrease in the erythroid elements in male and female rats. Liver weights were increased and thymus weights decreased as a function of D4 dose. These organ weight changes were more pronounced in the female.