1,1,1,2-Tetrafluoroethane (R-134a) is a non-ozone-depleting alternative to dichlorodifluoromethane for use as an air-conditioning refrigerant and as a propellant in anti-asthmatic and other pharmaceutical preparations. Hepatic microsomes, supplemented with NADPH, catalyzed the release of F- from R-134a; metabolite production was positively correlated with both duration of incubation and gas phase [R-134a]. Defluorination of R-134a was inhibited by CO, lack of NADPH, or heat denaturation of microsomes. Release of F- from R- 134a biotransformation as shown by the near-total lack of dehalogenation during anaerobic incubations. R-134a did not produce a difference spectrum (360 to 500 nm) with either oxidized or dithionite-reduced microsomes. Microsomes from phenobarbital- or Aroclor 1254-treated rats produced greater amounts of F- per mg protein from high concentrations of R-134a than did microsomes from untreated rats, but when normalized for microsomal cytochrome P-450 content both phenobarbital and Aroclor treatment decreased the specific activity (nmol F-/nmol cytochrome P-450) of R-134a metabolism. Furthermore, while defluorination of R-134a by microsomes from livers of untreated rats was substrate-saturable (Vmax, 11 nmol of F-/nmol cytochrome P-450/15 min; KM, 8% R-134a), R-134a dehalogenation by microsomes from Aroclor-treated rats was nonsaturable with [R-134a] as high as 69%. Microsomes from phenobarbital-treated rats retained the saturable, low KM activity, but also exhibited the apparently nonsaturable kinetic component when [R-134a] was greater than 24%.(ABSTRACT TRUNCATED AT 250 WORDS)