Hi Klaas,

Thank you for posting in the community.

I have researched the sample you provided and when the form is invalid, changing the selection once does not fire a postback. Changing the selection again, however does fire a postback (the form being invalid still).

Interestingly enough, the same behavior can be observed with an ASP Button with CauseValidation set to false. While the form is invalid, the button causes a postback only after the second click. In this scenario I can suggest that you enable the postback on value changing in your scenario as this seems to work regardless of form validity. 

Please let me know if this helps.

http://forums.asp.net/t/1554406.aspx

When Page_ClientValidate() is called and returns false, the Page_BlockSubmit variable is set to true, which blocks the first attempt of any control to postback. Setting the variable to false after validating the page on the client should therefore resolve the matter:

        function ToggleValid() {
            if (isValid == true) {
                document.getElementById('Button1').value = "SetValid"
                isValid = false;
            } else {
                document.getElementById('Button1').value = "SetInValid"
                isValid = true;
            }
            Page_ClientValidate();
            Page_BlockSubmit = false;
        }

Please let me know if this helps.