Topical application of caffeine for the treatment of neonatal apnoea was considered in 57 low birth weight infants (less than 1500 g birth weight). The rationale for the study was that transdermal absorption of drugs and chemical agents has been demonstrated in neonates depending on anatomical and functional immaturity of the epidermal barrier. Considering these issues we studied the efficacy of percutaneous application of caffeine using high pressure liquid chromatography (HPLC) for evaluation of its plasma levels. 2 x 7.5 mg (babies less than 1000 g, extremely low birth weight [ELBW] or 2 x 10 mg (babies greater than 1000 g, very low birth weight [VLBW]) of caffeine were applied transcutaneously in form of a gel to the abdominal skin (Standard dose = 0.06 g of gel equivalent to 10 mg of caffeine citrate). Gestational age of our patients was 29.4 +/- 1.7 weeks, mean birth weight 1025 +/- 240 g. Mean postnatal age at beginning of treatment was 25.5 +/- 18 h. Of the treated babies, 73% had serum levels in therapeutic range about 48 h after the first dose of caffeine application. After 10 doses 97% of patients had serum levels in the therapeutic range. We conclude that percutaneous caffeine application is a safe and useful approach for treatment of apnoea in VLBW and ELBW infants.