It has been shown for the azole antifungal agents, ketoconazole and DTP, that hepatic binding, is a major determinant of their volume of distribution and this observation is of particular interest in view of the well-documented avid binding of azoles to cytochromes P450. Whilst the hepatic binding characteristics of these two compounds are similar, their hepatic clearance differs markedly in terms of the rate of metabolism and the number and nature of metabolites produced. Fluconazole is a bis-triazole drug similar in structure to DTP but not subject to metabolism in rat. We have demonstrated by means of steady-state infusion studies the clearance of this azole (1.85ml/min/kg) to be independent of blood concentration over a 0.01-50mg/L range. Also fluconazole plasma protein binding is minimal (9.5%) and its blood:plasma ratio unity over a similar concentration range. Liver:blood partition coefficients for fluconazole are concentration dependent ranging from 30 to 2. The volume of distribution term is also nonlinear with concentration and can be correlated with the liver:blood partition coefficient. These findings are discussed together with earlier documented data on ketoconazole and DTP in terms of a tissue binding role for hepatic cytochromes P450. The similarity in behaviour of the hepatic partitioning of the three azoles contrasts markedly with the nature of (or lack of) hepatic metabolism.