L-ornithine is a non-essential, non-proteinogenic cationic amino acid. Its complex metabolic function causes a great interest in its pharmacotherapeutical potentials. L-orntihine is critical for the metabolism of keratinocytes, especially in synthesis of urea, polyamines and precursors of collagene. In this study we investigate in vitro the cytotoxicity of L-ornithine HCl and its influence of urea-synthesis and the expression of arginase and ornithine decarboxylase in native human keratinocytes. Further investigations evaluate the possibility of topical dermal application of L-ornithine HCl and its in vivo-toxicity using the hen's egg test chorio allantois membrane (HET-CAM) model. There is no toxic potential of L-ornithine HCl up to hundred times of physiological concentration. Higher concentrations induce apoptosis in native keratinocytes in a concentration- and time-dependend manner. In vivo L-ornithine HCl causes no vascular and no systemic reaction up to 100 mmol/L detectable by laser Doppler fluxmetry in the HET-CAM model. The dermal availability of L-ornithine after topical application of semi-solid standard-preparations containing 10 % L-ornithine HCl was investigated by using the FRANZ modell. Best results in the concentration-time-profil were received by the amphiphile system (Basiscreme DAC). Topical application seems to be possible. L-ornithine HCl decreases (> 1 mmol/L) the de novo urea synthesis of keratinocytes and increases (> 10 mmol/L) the expression of the urea-generating enzyme arginase (westernblot). Otherwise there is no influence on the expression of ornithine decarboxylase, the initial enzyme of polyamine synthesis.