A method for determination of drug substances solubility in lipophilic solvents is presented. The solubility was determined in lipophilic suppository bases meltings, in pharmaceutical lipoids as Oleum Ricini, Oleum Arachidis, Cera perliquida, Paraffinum perliquidum and in chemically defined lipoids as n-hexadecane, 1-hexadecane, cetylic alcohol, palmitic acid, cetylpalmitate. Consequences from chemical constitution of substances for solubility are discussed, also consequences from chemical constitution and dielectric constants of lipoidic solvents for their solution behavior. For the substances investigated, the apparent partition coefficients in the two-phase systems lipoid/phosphate buffer pH 7,4 and n-octanol/phosphate buffer pH 7,4 were determined, also the solubility in phosphate buffer. The results show, that connections between partition coefficients and solubility in lipophilic or aqueous phases do not exist. On the other hand, an indirect proportionality between water solubility and lipoid solubility also does not exist. In consequence, interpretations of drug release from lipophilic systems have to be proceeded from exact knowledge of partition behavior and solubilities in both the lipophilic and aqueous phase.