This study investigates the effect of intraperitoneal injection of L. bulgaricus and S. thermophilus on interferon production by Swiss mice. The serum from mice given 5 x 10(7) L. bulgaricus in 0.5 ml saline showed a maximal production of 300 U/ml of alpha/beta interferon activity six hours after injection. Cellular integrity appears to be necessary for stimulation; heat-treated bacteria had little effect, while irradiated-bacteria had a greater effect. TNF was also produced, the sera of mice with high IFN also contained 300 U/ml TNF. Streptococcus thermophilus produced no detectable increase in serum IFN, but the 2'-5' A synthetase activity of peritoneal cells was elevated suggesting that small amounts of interferon were produced. Injection of Streptococcus thermophilus plus Lactobacillus bulgaricus did not change the serum interferon response to L. bulgaricus. These observations suggest that non-pathogenic bacteria such as those used in food processing, can stimulate IFN production in mice. There is some evidence that the bacterial cell walls might be responsible for at least part of this effect.