Direct photolysis and solar TiO(2) photocatalysis of Trimethoprim (TMP) in different water matrices (demineralised and simulated seawater) have been studied. Direct photolysis yielded a similar, slow TMP degradation rate in both water matrices, and the formation of very stable photo-transformation products. Dissolved organic carbon decreased slightly after prolonged irradiation. The main intermediate identified was a ketone derivative (trimethoxybenzoylpyrimidine), which was proved to be a photosensitizer of TMP degradation. During TiO(2) photocatalysis, TMP was completely eliminated in both water matrices at a similar rate, however, the mineralization rate was appreciably reduced in seawater, which can be explained by the presence of inorganic species acting as hydroxyl radical scavengers, and directly affecting photocatalytic efficiency. Identification of intermediates showed differences between the two processes but hydroxylation, demethylation and cleavage of the original drug molecule were observed in both.