Notes: Abstract The Miocene-Pliocene Macusani ash-flow tuffs from SE Peru, containing magmatic andalusite and muscovite, have homogeneous major element compositions, with a narrow range of SiO2 (71–74 wt%), high Al2O3 (normative corundum 〉2%; A/CNK〉1.2) and alkalis, and low FeOt, MgO, CaO, TiO2. P2O5, F, Li2O, and B2O3 are also high. The associated obsidian glasses are more felsic and peraluminous and extremely enriched in F, P, Li and B compared to the ash-flow tuffs. These are compositionally similar to Himalayan or Hercynian two-mica granites and the obsidian glasses to some rare fractionated members of the two-mica granite series. Both ash-flow tuffs and obsidian glasses show enrichments in lithophile trace elements (Be, Zn, As, Rb, Nb, Sn, Sb, Cs, Ta, W, U) and depletions in Cl, S, Sc, V, Cr, Co, Ni, Cu, Y, Mo, Hf. REE patterns for the ash-flow tuffs are fractionated (La/Lu n =13-26) with a moderate Eu anomaly and they contrast with patterns for the obsidian glasses characterized by lower total REE, lower La/Lu n and Eu/Eu*. Sr(87Sr/86Sr initial ratio= 0.721–0.726), Pb (206Pb/204Pb=18.74–19.45; 207P/204Pb= 15.66–15.72) and Nd isotopic compositions (ɛ Nd=-8.96 to-9.35) are typically crustal. Oxygen isotopic compositions are high in 18O (glasses:δ18O=+12‰; quartz:δ18O=+ 11.5 to +12.7‰). Batch melting of isotopically heterogeneous source rocks is suggested by the Sr and Pb data. In contrast to major elements, trace elements demonstrate compositional differences between erupted magmas. The last erupted magmas are less fractionated relative to the first erupted. The Macusani magmas are direct products of crustal melting. There is no evidence for mixing or assimilation by a foreign, meta- to sub-aluminous magma, although mafic magmas are considered to be likely sources of heat for melting. Source rocks dominantly consisted of metapelites. Models of magma generation based on external control of $$a_{H_2 O}$$ (H2O for melting being supplied by aqueous fluids percolating in the source region) fail to account for a number of features of the Macusani magmas. $$a_{H_2 O}$$ was internally controlled and magma generation resulted essentially from fluid-absent melting of F-muscovite combined with incipient biotite dehydration. Fluid-absent melting of F-rich muscovite occurs at higher temperatures than for pure OH-muscovite and generates a H2O-undersaturated melt. Incipient melting of biotite resulted from high heat flux and elevated temperatures (up to 800° C) in the source region. The Macusani magmas are generated as low melt fraction batches (15 vol%).