Isoprene photooxidation is a major driver of atmospheric chemistry over forested regions. Isoprene reacts with hydroxyl radicals (OH) and molecular oxygen to produce isoprene peroxy radicals (ISOPOO). These radicals can react with hydroperoxyl radicals (HO2) to domi- nantly produce hydroxyhydroperoxides (ISOPOOH). They can also react with nitric oxide (NO) to largely produce methyl vinyl ketone (MVK) and methacrolein (MACR). Unimolecular isomerization and bimolecular reactions with organic peroxy radicals are also possible. There is uncertainty about the relative importance of each of these pathways in the atmosphere and possible changes because of an- thropogenic pollution. Herein, measurements of ISOPOOH and MVK + MACR concentrations are reported over the central region of the Am- azon basin during the wet season. The research site, downwind of an urban region, intercepted both background and polluted air masses during the GoAmazon2014/5 Experiment. Under background condi- tions, the confidence interval for the ratio of the ISOPOOH concentra- tion to that of MVK + MACR spanned 0.4–0.6. This result implies a ratio of the reaction rate of ISOPOO with HO2 to that with NO of approx- imately unity. A value of unity is significantly smaller than simulated at present by global chemical transport models for this important, nom- inally low-NO, forested region of Earth. Under polluted conditions, when the concentrations of reactive nitrogen compounds were high (>1 ppb), ISOPOOH concentrations dropped below the instrumental detection limit (<60 ppt). This abrupt shift in isoprene photooxidation, sparked by human activities, speaks to ongoing and possible future changes in the photochemistry active over the Amazon rainforest.