The lethal response of asynchronous exponentially growing mouse lung (L1A2) cells heated to 42 degrees C under hypoxic conditions was demonstrated in vitro. Acutely hypoxic cells (i.e. heated immediately after 30 min of N2 plus CO2 gassing) and aerobic cells treated under the same extracellular pH were equally sensitive to a single hyperthermic treatment, and incubation under hypoxia for up to 24 hours prior to treatment did not influence cell survival. Similarly, under controlled pH conditions (pH within 7.0 to 7.4) recovery from hyperthermic damage demonstrated by two-dose hyperthermic fractionation (each of 1.5 hours at 42 degrees C) was identical in hypoxic and aerobic cells, and the highest recovery was found at a 10-hour interval. Preheating for 1.5 hours at 42 degrees C induced thermal resistance to a second treatment at 42 degrees C (thermotolerance). At the 10-hour interval the degree of thermotolerance was not influenced by incubation under hypoxic conditions (thermotolerance ratio, TTR equals 4.7 in both aerobic and hypoxic cells). The data indicate that hypoxic conditions do not influence the heat response in L1A2 cells to either a single or a two-dose fractionated hyperthermic treatment in which hypoxia or aerobic conditions were maintained in the interval between the heat treatment.