Members of the biologically active series tetracyclines (TCs) suffer visible-light-promoted photodynamic degradation to different extents, depending on their respective chemical structures and reaction conditions (solvent polarity and pH) The photo-oxidation is accompanied by a partial loss of the antimicrobial power. The photodamage is very fast in the alkaline pH range and less aggressive, although not negligible in kinetic terms, in the physiological pH region. Photo-oxidation quantum efficiencies, evaluated for eight TC derivatives, through singlet molecular oxygen [ 02( 'h,) ] phosphorescence detection, spectrophotometric and polarographic methods, range from 0. I2 to 0.65 as upper limits in alkaline medium. The photo-oxidation essentially proceeds via a 02( 'Q-mediated process. with rose bengal or eosine as dyesensitizers. Nevertheless, as a minor reactive pathway, the excited triplet state of the dye sensitizers interacts with TCs in a competitive process with O,( 'An) generation. The O,( '&,)-mediated photo-oxidation of TCs appears to be a plausible mechanism to account for their phototransformations in biological media, in the presence of visible-absorbing pigments. In both highly and moderately polar media, the quenching of the excited oxygen species is mainly represented by a reactive interaction. It is exerted by the TC molecule through a cooperative effect from the different contributions of several nuclear and extranuclear 02( 'A,)-sensitive substituents, as discussed in detail in this paper. The TC phenolic function plays the driving role as a 02( 'Q-quencher only at pH values higher than 9. The quantum yields for 02( I&) generation ( @Jo) by TCs, upon direct photo-irradiation, have also been investigated. This family of compounds possesses extremely poor @A values, lower than 0.03 in the most favourable cases. Nevertheless, the TC photoproduct, formed through direct irradiation, efficiently generates OZ( '&) with @A = 0.24. This important finding constitutes the first direct evidence of Type II sensitization by TC photoproducts, and could contribute to the elucidation of the mechanism of TC phototoxicity.