The assessment of the experimental setup and of the data processing methods for the in vivo kinematic investigation of the human joints is described here. The relative movement of contiguous body segments, supposed rigid, is described by means of the instantaneous helical axis (IHA). Great attention has been paid to the stereophotogrammetric aspects and to the filtering and numerical differentiation procedures, in order to obtain reliable estimation of IHA parameters. Their accuracy has been estimated in a simulation context. One experimental case relative to the metacarpophalangeal (MCP) joint is described in detail. The clinical application of the procedures and of the experimental protocol has been used in the entire work.