We report the use of multiphoton-excited photochemistry to generate highly fluorescent products from hydroxyindoles fractionated in submicron capillary electrophoresis channels. In this approach, the near-infrared (750 nm) output from a modelocked titanium:sapphire laser is focused at the outlet of a 0.6-m i.d. capillary, producing pulse intensities of Ο³10 12 W cm Ψ2 within a femtoliter focal volume. Hydroxyindole molecules migrating through the outlet aperture of the capillary intersect the beam focus, where absorption of three to four photons (Ο³1.65 eV photon Ψ1 ) initiates a photobleaching reaction. The resultant hydroxyindole photoproducts produce broadband visible emission ( max Ο· 500 nm) when excited with two additional near-IR photons and appear substantially more resistant to photobleaching than the parent hydroxyindoles. This multiphoton-induced conversion of analytes to hyperluminescent derivatives thus offers a more sensitive approach than UV fluorescence for detecting extremely small quantities of material. Mixtures of the hydroxyindoles serotonin (5-hydroxytryptamine), 5-hydroxytryptophan, and 5-hydroxyindole acetic acid are reliably characterized (relative error Ο·10%) in 100 s, with detection limits as low as Ο³70 zmol (Ο³42,000 molecules). The sensitivity of this measurement strategy improves on the best previously reported results for capillary separations of indoles by more than one order of magnitude.