The Bessel-type functions, structured as extensions of the classical Bessel functions, were defined by Everitt and Markett in 1994. These special functions are derived by linear combinations and limit processes from the classical orthogonal polynomials, classical Bessel functions and the Krall Jacobi-type and Laguerre-type orthogonal polynomials. These Bessel-type functions are solutions of higher-order linear differential equations, with a regular singularity at the origin and an irregular singularity at the point of infinity of the complex plane. There is a Bessel-type differential equation for each even-order integer; the equation of order two is the classical Bessel differential equation. These even-order Bessel-type equations are not formal powers of the classical Bessel equation. When the independent variable of these equations is restricted to the positive real axis of the plane they can be written in the Lagrange symmetric (formally self-adjoint) form of the Glazman–Naimark type, with real coefficients. Embedded in this form of the equation is a spectral parameter; this combination leads to the generation of self-adjoint operators in a weighted Hilbert function space. In the second-order case one of these associated operators has an eigenfunction expansion that leads to the Hankel integral transform. This article is devoted to a study of the spectral theory of the Bessel-type differential equation of order four; considered on the positive real axis this equation has singularities at both end-points. In the associated Hilbert function space these singular end-points are classified, the minimal and maximal operators are defined and all associated self-adjoint operators are determined, including the Friedrichs self-adjoint operator. The spectral properties of these self-adjoint operators are given in explicit form. From the properties of the domain of the maximal operator, in the associated Hilbert function space, it is possible to obtain a virial theorem for the fourth-order Bessel-type differential equation. There are two solutions of this fourth-order equation that can be expressed in terms of classical Bessel functions of order zero and order one. However it appears that additional, independent solutions essentially involve new special functions not yet defined. The spectral properties of the self-adjoint operators suggest that there is an eigenfunction expansion similar to the Hankel transform, but details await a further study of the solutions of the differential equation. © 2004, Taylor & Francis Group, LLC.