The effects of carbon loading and endcapping on the solid-phase extraction onto C18 bonded silica gel of a range of beta-blockers from aqueous buffer and from dog plasma has been investigated. The highest extraction efficiencies were obtained for those phases with carbon loadings of between 5 and 16% for phases without endcapping or 10.5-14% for endcapped material. With carbon loadings of 18 and 22% (plus endcapping) poor extractions from the matrix were obtained combined with further losses at the wash steps. Matrix effects were observed with dog plasma which accentuated the effects seen with buffer. These results are best explained by assuming that a cationic interaction of the secondary amino group present in the analytes with residual silanols on the silica surface is primarily responsible for the extraction of these analytes.