Fluoride pollution in drinking water is an international problem as the fluoride present is often at levels above acceptable limits. In the studies reported here, sodium fluoride (NaF) treatment of rats by gavage for 28 days resulted in the induction of oxidative stress and immunotoxicity. It was shown here that NaF treatment lowered cellular immunity in the rats as illustrated by a significant diminution in peripheral blood lymphocyte, monocyte and neutrophil counts in conjunction with a reduction in splenocyte counts. Effects of NaF treatment on humoral immunity were reflected here in a lowering of the levels of plasma IgG specific to a test antigen (i.e., bovine serum albumin). Disorganization in the histoarchitecture was also noted in the host spleen and thymus after NaF treatment. To determine if oxidative stress was among the potential possible causes for the observed induced immunotoxicities, catalase and peroxidase activities along with malondialdehyde (MDA, product of free radical damage to cells) levels in the spleen and peripheral blood packed cells were also measured. The results indicated that there was a significant diminution in the activities of both the enzymes along with an elevation in MDA levels in both the tissues in treated rats. This report highlights the proposition that chronic exposure to fluoride contaminated drinking water is likely to result in immunotoxicity and, furthermore, that the damage to primary immune organs is due to an induction of oxidative stress.