Environmental concerns have dictated the replacement of CFC-12 refrigerant with HFC-134a in automotive air-conditioning (A/C) systems. Since polyglycols are synthetic compounds compatible with HFC-134a and considered as lubricants for the A/C compressor, interations of HFC-134a with glycol-type compounds and thermodynamic properties of the solutions are important in designing an A/C system. In this work, the solubility of HFC-134a in four glycol-type compounds was measured at −5 to 80°C and 90 to 960 kPa. HFC-134a had the greatest solubility in tetraethylene glycol dimethyl ether. HFC-134a was less soluble in hexylene glycol and tetraethylene glycol and least soluble in triethylene glycol. Mixtures of HFC-134a with TRIG or TGDE showed phase separation. Solubility data were used to calculate the activity coefficient of HFC-134a in glycol solutions. An equation of the form, lnγr = (1 − xr)[A + Bxr], was found to correlate γr to the mole fraction of HFC-134a in the solution where A and B are constants which may depend on the temperature. Based on a model assuming a specific interaction between molecules and using the activity of HFC-134a, a higher degree of interaction is expected between HFC-134a and tetraethylene glycol dimethyl ether molecules than between the molecules of HFC-134a and other glycols. In general, glycols with free -OH groups may have less affinity for HFC-134a. Solubility is discussed in terms of its parameters and chemical structure of the glycols, as well as the effect of temperature on the solubility, the activity coefficient, and the thermodynamic properties of the HFC-134a/glycol solutions.