Capacity factors are determined for a set of drugs for which human oral absorption (HOA) data are available, using immobilized artificial membrane (IAM) chromatography. The compound set represented acidic, basic, neutral and amphoteric drugs from various structure classes and having low to high human oral absorption. Effect of mobile phase pH on retention was investigated to determine the optimal condition for better correlation with HOA. The retention (capacity factor, k'(IAM) of each drug was measured by reverse phase HPLC using an IAM.PC.DD2 (1 cm x 3 mm i.d., 12 microm) column with an eluent of acetonitrile - 0.01 M phosphate buffer at pH 4.5-7.4. The pH dependent k'(IAM) was in accordance with pH partition theory. Using non-linear regression analysis the obtained log k'(IAM) values were compared with published data on HOA in order to establish correlation. The better correlation with HOA was observed when the highest log k'(IAM) value selected among pH 4.5-7.4 (R(2)=0.8566) for each drug rather than obtained at more traditional pH 7.4 (R(2)=0.7403). Finally, it was confirmed by Cook's D outlier test that there was no influential observation in the model that affect the relationship between IAM capacity factor and HOA. The assay conditions were optimized and validated to make it suitable for routine analysis and for compound characterization in early discovery where permeability may be an issue.