We report pyrene fluorescence probe experiments which examine the association in aqueous solution of a hydrophobically modified hydroxyethylcellulose (HMHEC) of M w ≈ 300 000 containing on average 1 C16H33 group/143 anhydroglucose units as well as the transformation of this polymer into a pyrene-labeled derivative HMHEC-Py-1 containing 1 pyrene/200 glucose units. Fluorescence studies of mixtures of HMHEC-Py-1 + HMHEC in water demonstrate that both pyrene−pyrene and pyrene−C16 associations occur, and we are able to infer that even in the most dilute solutions that we can examine these polymers exist as small aggregates of several polymer molecules. HMHEC-Py-1 exhibits excimer emission at concentrations as low as 0.01 g/L. As the polymer concentration is increased, one observes a sharp increase in the reduced viscosity at 1.5−2.0 g/L. Over the same range of concentrations HMHEC-Py-1 exhibits an increase in I E/I M values, indicating that the viscosity increase is due to a substantial increase in polymer association. HMHEC solubilizes pyrene as a fluorescent probe. The limiting solubility, approximately 1 pyrene/35 C16 alkyl groups, and the partition coefficient (5 × 104) are much smaller than those found for other more flexible associating polymers, yet the I 1/I 3 value is consistent with solubilization of pyrene in domains large enough to minimize exposure of the probe to water. We infer that HMHEC in water forms hydrophobic domains with a large size polydispersity. The mean aggregate size is small, but hydrophobic probes such as pyrene and bis(1-pyrenylmethyl) ether are solubilized preferentially in the largest hydrophobic domains.