Eight cultivars each of red and green leaf lettuce were raised in a greenhouse with supplemental UV radiation, either UV-A (wavelengths greater than ca. 315 nm) or UV-A+UV-B (wavelengths greater than ca. 290 nm; 6.4 kJ m-2 daily biologically effective UV-B), or no supplemental UV (controls). Several phytonutrients were analyzed in leaf flours to identify lines with large differences in composition and response to UV-B. Red leaf lettuce had higher levels of phenolic acid esters, flavonols and anthocyanins than green lines. Both green and red lines exposed to UV-B for 9 days showed 2-3-fold increases in flavonoids compared to controls, but only 45% increases in phenolic acid esters, suggesting these compounds may be regulated by different mechanisms. There were large differences between cultivars in levels of phenolic compounds under control conditions and also large differences in UV-B effects. Among red varieties, cv. Galactic was notable for high levels of phenolics and a large response to UV-B. Among green varieties, cvs. Black-Seeded Simpson and Simpson Elite had large increases in phenolics with UV-B exposure. Photosynthetic pigments were also analyzed. Green leaf lettuce had high levels of pheophytin, a chlorophyll degradation product. Total chlorophylls (including pheophytin) were much lower in green compared to red varieties. Lutein, a carotenoid, was similar for green and red lines. Total chlorophylls and lutein increased 2-fold under supplemental UV-B in green lines but decreased slightly under UV-B in red lines. Lettuce appears to be a valuable crop to use to study phytochemical-environment interactions.