The size and the shape of caldesmon as well as its 50-kDa central and 19-kDa C-terminal fragments were investigated by photon correlation spectroscopy. The hydrodynamic radii, which have been calculated from the experimentally obtained translational diffusion coefficients, are 9.8 nm, 6.0 nm, and 2.9 nm, respectively. Moreover, the experimental values for the translational diffusion coefficients are compared with results obtained from hydrodynamic model calculations. Detailed models for the structure of caldesmon in solution are derived. The contour length is about 64 nm for all of the models used for caldesmon.