The response of plants to stress such as UV-radiation or drought highly depends on the species, cultivar, plant organ, developmental stage, and furthermore, is influenced by ecophysiological interactions. Drought stress as well as UV irradiation are the most adverse factors for plant growth and productivity. In the present study, the interactive effect of UV-B and drought stress on biomass, primary and secondary metabolites, and mediated enzyme activity of phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) was investigated in lettuce (Lactuca sativa L.). It was found that biomass production decreased in response to both stressors, while dry matter, total phenolic contents and the flavonol quercetin were not significantly affected by UV-B and drought stress, neither solely nor in combination. In contrast, anthocyanins and luteolin accumulated only in response to drought stress. However, the precursor amino acid proline as well as the activity of PAL increased under conditions of increased UV-B and water deficit. Thus, the present results deduce that both stressors acted either synergistically or to some extent antagonistically in terms of inducing plant protective mechanisms