Ammonium chloride (NH4Cl) was found to markedly inhibit the ability of cultured human fibroblasts to establish an antiviral state following exposure to poly IC. This antiviral state was diminished by the simultaneous addition of as little as 200 microgram/ml of NH4Cl. The effects of ammonia on the superinduction of human fibroblast interferon (IFN-beta) were also investigated. The titer of IFN dropped from 2600 units/ml in control cultures, to less than 50 units/ml in the presence of 400 microgram/ml of NH4Cl. A critical stage sensitive to ammonia was within the first 15 minutes following addition of poly IC.