BACKGROUND: Although non-adherence to an immunosuppressive regimen (NAH) is a major risk factor for poor outcome after renal transplantation (RTx), very few studies have examined non-adherence intervention in this context. This pilot randomized controlled trial (RCT) tested the efficacy of an educational-behavioural intervention to increase adherence in non-adherent RTx patients. We also assessed how NAH evolves over time. METHODS: Eighteen RTx non-adherent patients (age: 45.6 +/- 1.2 yr; 78.6% male) were randomly assigned to either an intervention group (IG) (n = 6) or an enhanced usual care group (EUCG) (n = 12), the latter receiving the usual clinical care. The IG received one home visit and three telephone interviews. We assessed NAH through electronic monitoring (EM) of medication intake during a nine-month period (three months intervention, six months follow-up). RESULTS: Five of 18 patients withdrew. Inclusion in the study resulted in a remarkable decrease in NAH in both groups over the first three months (IG chi(2) = 3.97, df = 1, p = 0.04; EUCG chi(2) = 3.40, df = 1, p = 0.06). The IG showed the greatest decrease in NAH after three months, although this did not reach statistical significance (at 90 d, chi(2) = 1.05, df = 1, p = 0.31). Thereafter, NAH increased gradually in both groups, reaching comparable levels at the end of the six-month follow-up (i.e. at nine months). CONCLUSION: Our findings suggest an inclusion effect. Although the intervention in this pilot RCT appeared to add further benefit in medication compliance, a lack of statistical power prevented us from making a strong statistical statement.